‘Blinking’ DNA probes revolutionize optical microscopy

Researchers are developing probes that highlight the goings on inside cells at a super high resolution at Wyss Institute for Biologically Inspired Engineering of Harvard University in Boston.

The institute announced Oct. 3 that it has garnered a $3.5 million grant, the Transformative Research Award, from the National Institutes of Health (NIH) to create the affordable and user-friendly microscopy technique that renders moot previous challenges in microscopy. DNA microscopy endeavors to differentiate between healthy and diseased cells and track the functions of key components within them that provide structure, movement and the activation of genes.

"If you want to study physiology and disease, you want to see how the molecules work, and it's important to see them in their native environments," said Peng Yin, PhD, a researcher at Wyss Institute and assistant professor of systems biology at Harvard, in a release.

Conventional light microscopes fail to distinguish cells past the 0.2 micrometer mark—or approximately one five-hundredth the width of a single strand of human hair, because of the properties of light and its diffraction limit. New nano-DNA probes would uncover the inner-workings of cell receptors, RNA, DNA and enzymes for groundbreaking biomedical research.

Scientists at the Wyss Institute call the new technique “DNA-PAINT” and use structures called imager strands that are essentially sections of DNA marked with fluorescent dye. The imager strand attaches to the matching DNA strand on a targeted molecule and bond creates a blinking effect that breaks through the known diffraction limit to produce clear, simultaneous nanoscale images of multiple aspects of cell biology that allow biomedical researchers to witness complex physiological functions firsthand.

"The powerful thing about using DNA lies in its amazing programmability," said Yin. "We plan to use that capability to make molecules in cells blink in a programmable and autonomous way. This will allow us to see things that were previously invisible."