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The page below is a sample from the LabCE course Troubleshooting Guidance for Hematoxylin and Eosin (H&E) Stain. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Bubbling is typically caused by water beneath the tissue section that turns to vapor
when placed in the oven. The steam goes through the tissue, causing coagulation
of proteins. Expired fixatives can also cause this same artifact.

Nuclear Bubbling: Created After Cutting

Nuclear bubbling occurs when the proteins in the nucleus coagulate. This artifact is often a result of poorly fixed samples that have encountered a high level of heat. After sectioning, wet slides are often placed in an oven to dry. High temperatures (eg, 70°C) can cause the water under the section to rapidly evaporate through the tissue. The evaporation can cause the proteins to coagulate, giving the soap bubble artifact. The best way to avoid bubbling in this case is to either lower the oven temperature or allow the slides to somewhat airdry prior to placing them in the oven.