The HybriWell hybridization sealing system is a coverslip—seal combination that forms chambers optimized for in situ hybridization work. Each disposable incubation chamber seals securely to a microscope slide, providing a limited-volume chamber for reagent addition. Solutions are easily added through dual-access ports without disrupting the specimen. The hydrophobic coverslips are nuclease free and will not trap or bind probes, allowing uniform distribution of the reagent over the specimen. The HybriWell sealing system also includes a quick-seal tool to secure the hydrophobic cover to the microscope slide, as well as nuclease-free adhesive seal tabs to cover the access ports (seal tabs are also available separately).