Using a DNA-tagging technique instead of immunohistochemistry, researchers were able to produce 10 nm resolution STORM images labeling four distinct cellular structures -with four different colors – in a single fixed cell. The technique was developed by Peng Yin’s lab at Harvard’s Wyss Institute for Biologically-Inspired Engineering.
The researchers label a particular biomolecule they want to image with a short DNA tag, then add to the solution a complementary DNA strand carrying a fluorescent dye that lights up only when the two strands pair-up, and goes dark when they separate, causing the biomolecule to “blink” at a precise rate the researchers can control. The rapid blinking facilitates STORM super-resolution microscopy techniques that can penetrate the 200 nm diffraction limit of optical microscopy. Researchers then target a new DNA sequence conjugated with a different fluorescent dye to a second biomolecule, and then a third, and so on, then overlay the resulting images to create a composite image in which cellular structures made up of these different biomolecules are color-coded. The technique, dubbed “Exchange PAINT” is an extension of “DNA PAINT,” a technique that tackled one color STORM imaging with DNA tagging. The research was published yesterday in Nature Methods.