The invention that first enabled researchers to see clear images of living cells was the phase-contrast microscope, which won its inventor, Frits Zernike, a Nobel Prize in 1932. Prior to Zernike's work, specimens were typically stained with organic dyes with such colorful names as coomassie blue and malachite green. These dyes either stained the whole specimen to provide contrast or, preferably, stained only parts of cells, allowing researchers to look at specific cellular components like the nucleus and cell membranes. Fixing and staining specimens, however, killed the cells and distorted their appearance.
Following Zernike's invention, another contrast-generating microscope, the differential interference-contrast microscope, was invented by G. Nomarski in 1952. In the ensuing four decades, contrast microscopes have become standard equipment in cell biology laboratories. "The best way to look at living cells today is using phase- contrast or differential interference- contrast microscopy," says neurobiologist Christopher Case of the State University ...