The plaque assay is originally a virological assay developed to count and measure infectivity of bacteriophages. Later, it was applied to count mammalian viruses as well. The plaque assay remains to be the most widely used technique for virus isolation and purification, and to determine viral titers. The basis of the technique is to measure the ability of a single infectious virus to form a “plaque” on a confluent monolayer culture of cells. A plaque is formed as a result of infection of one cell by a single virus particle followed by the replication of that virus, and eventually, the death of the cell. The newly replicated virus particles will then infect and kill surrounding cells. The culture will then be stained with a dye, which stains only viable cells but not the dead cells. Hence, the dead cells in the plaque will appear unstained against the colored background.
Nowadays, the plaque assay is applied to detect cells producing antibodies that destroy erythrocytes (by hemolysis). The basis is the clear plaque that indicates the red blood cells have been hemolysed by the antibodies.