Many of the secrets of cancer and other diseases can be found in the cell's nucleus. But getting to that level – to see and investigate the important genetic material housed there – requires creative thinking and extremely powerful imaging techniques.

Vadim Backman and Hao Zhang, nanoscale imaging experts at Northwestern University, have developed a new imaging technology that is the first to see DNA "blink" or fluoresce. The tool enables the researchers to study individual biomolecules as well as important global patterns of gene expression, which could yield insights into cancer.

It features six-nanometer resolution and is the first to break the 10-nanometer resolution threshold. It can image DNA, chromatin, and proteins in cells in their native states, without the need for labels.

For decades, textbooks have stated that macromolecules within living cells, such as DNA, RNA, and proteins, do not have visible fluorescence on their own.

"People have overlooked this natural effect because they didn't question conventional wisdom," said Backman, the Walter Dill Professor of Biomedical Engineering in the McCormick School of Engineering. "With our super-resolution imaging, we found that DNA and other biomolecules do fluoresce, but only for a very short time. Then they rest for a very long time, in a 'dark' state. The natural fluorescence was beautiful to see."

Backman, Zhang, and collaborators are using their technique to study chromatin – the bundle of genetic material in the cell nucleus – to see how it’s organized. Zhang is an associate professor of biomedical engineering at McCormick.

"Insights into the workings of the chromatin folding code, which regulates patterns of gene expression, will help us better understand cancer and its ability to adapt to changing environments," Backman said. "Cancer is not a single-gene disease."

Current technology for imaging DNA and other genetic material relies on special fluorescent dyes to enhance contrast when macromolecules are imaged. These dyes may perturb cell function, and some eventually kill the cells – undesirable effects in scientific studies.

In contrast, the Northwestern technique, called spectroscopic intrinsic-contrast photon-localization optical nanoscopy, allows researchers to study biomolecules in their natural environment, without the need for these fluorescent labels.