A fundamental issue in all microarray experiments is background correction, which aims at reducing noise in background quantification. Signal intensities are generally quantified by subtracting the foreground intensities with the local background intensities, which are measured as the background signals immediately surrounding the spot of interest (termed here the 'adjacent background'; Figure 2b ). However, in protein microarrays local background regions can be easily skewed by artifacts such as small speckles. In addition, strong positive signals from on-chip kinase assays tend to produce signal smears on both film and phosphoimagers that exceed the normal feature size (Figure 2a) . In both cases, the measurement for that spot will be inaccurate. First, the background intensity will be arbitrarily high, which will diminish the real signal intensity for that spot. Second, the intensities will be affected by the alignment of the grid and extent of the smear, and, therefore, the variance of the same protein at replicate experiments will be increased.