Optical microscopists may soon have another option for generating photons for their imaging experiments. Researchers at Zhejiang University and Harbin University report a method for imaging, powered by electrochemistry or bioluminescence, that can be used to observe live cells at a high resolution for days (Nature 2026, DOI: 10.1038/s41586-026-10889-7).
Biochemists typically use fluorescent molecules to label cells. They then use a laser to excite the molecule before it spits a photon back out to return to its ground state. The result is a strong signal, but the laser also creates background noise, and it can damage the cell that is being looked at.
Electrochemical luminescence (ECL) produces photons from a chemical reaction, but the light it produces is dim compared with fluorescence. Still, because it doesn’t require laser excitation, it boasts lower background noise, and enzyme-catalyzed bioluminescence is gentler on cells. These advantages inspired Jiandong Feng and colleagues to attempt, in Feng’s words, to “increase the photon budget” for ECL in cells.
The team started with the photochemical workhorse compound ruthenium tris(bipyridine), which emits photons when it and coreactant tripropylamine encounter electricity. Replacing tripropylamine with a bis-tris coreactant yielded about 1,000 times more light.
The brighter reaction allowed the researchers to tackle the resolution problem inherent to light microscopy: any two objects that are closer together than the wavelength of the light used to image them will blur together to appear as a single point. Superresolution fluorescence techniques overcome this challenge in part through image processing, but those algorithms are not suitable for luminescent images. Instead, Weisong Zhao writes in an email to C&EN, “we developed an entropy-weighted correlation reconstruction strategy to extract super-resolution information from weak, reaction-driven luminescence fluctuations.”
Using antibody labels conjugated to the ruthenium complex, the researchers could resolve individual microtubules as little as 100 nm apart in a fixed cell.
The researchers also applied their image analysis method to bioluminescence—light-producing reactions that an enzyme can catalyze in a live cell. In cells engineered to let the enzyme luciferase hand off energy to a fluorescent protein, the researchers could image mitochondria every second for over 24 h.
Laurel Oldach is a senior editor and life sciences reporter at C&EN.
