Microscopic photos of cells just got clearer

A research team led by Feng Jiandong of Zhejiang University and Zhao Weisong of Harbin Institute of Technology has developed a novel high-resolution imaging technique to produce pictures of living cells using luminescent light emitted by the cells themselves.

Their chemically driven approach offers a new way to observe living cells by using extremely long imaging times in a way that doesn't damage the cell samples being photographed.

Almost all modern microscopy and analytical instruments employ a basic detection sequence using external illumination. Fluorescence microscopes use laser light to excite fluorescent molecules; electron microscopes use high-energy electron beams to resolve fine structures; and infrared spectrometers use infrared radiation to identify chemical bonds.

For more than a century, these have enabled scientists to decode a microscopic world invisible to the human eye.

But external light excitation comes with a cost. The energy used to illuminate microscopic biological structures can alter or damage the samples being photographed, which is particularly significant in studies of living cells.

Researchers wanted to find out whether light generated naturally by the internal chemical reactions of cells could be used for imaging while avoiding cell damage. It was a formidable challenge.

With conventional fluorescence microscopy, images of fluorescent molecules can be captured 12 minutes after laser irradiation. "But the increased laser power can cause irreversible damage to cell viability," said Zhu Wenxin, a postdoctoral researcher at Zhejiang University and the first author of a paper describing the new imaging technique.

The team's alternative method, developed over many years, instead extracts high-resolution structural information from the faint light generated within cells, and without the damage caused by external illumination.

"Our technique allows continuous super-resolution observation for up to 41 hours, while the cells remain in good condition and the images stay clear," Zhu said, adding the dramatic increase in observation time could bring a qualitative change to the imaging of living cells and open up broader applications.

The breakthrough was made possible by an interdisciplinary collaboration integrating chemistry, optics, biology and computational science.

Feng, the team leader, dubbed the technique "RIED" (pronounced "reed"), an acronym for reaction-enabled super-resolution imaging via entropy-weighted correlation combined with deconvolution.

"I hope it can help us better read the microscopic processes of life," Feng said.