What are the disadvantages of using dried milk as a blocking buffer?

One limitation is that dried milk shouldn’t be utilized as a blocking agent when detecting phosphorylated proteins because it contains phosphoprotein casein. This component can interact with the antibody, leading to non-specific binding and increased background signal. Filtering may also be necessary to remove particulates from the solution to prevent them from binding to the membrane, which could cause a speckled background during detection. One should also avoid using dried milk if avidin-biotin detection systems are utilized since milk naturally contains biotin. Dried milk also decreases the sensitivity of certain commercially available anti-His monoclonal antibodies.