Multicolor Activated Fluorescent Dyes Thanks to Single Atom Replacement

Fluorescent dyes have transformed biomedical science. The Nobel Prize in Chemistry for 2008, for example, was given for the discovery and development of green fluorescent protein, GFP. Ever since GFP became available, scientists have been working on improving fluorescent dyes to better study dynamic processes within biological tissues.

Typically, ultraviolet light is used to activate such dyes, but this can be damaging to cells and even trigger them to behave in a certain way, potentially affecting experimental data. Moreover, many long-term experiments are not possible since the cells end up dying before the results come in.

Now, researchers at Rice University have come up with a way to make a variety of fluorescent dyes that are triggered by visible light that doesn’t have much influence on most living cells. This would allow for long-term super-resolution studies of living cells and tissues, opening a much wider door for the entire field of biomedicine.

The technology relies on replacing one atom of sulfur with an oxygen atom within commonly used fluorophores. This gives those fluorophores the ability to turn on and off in response to lower energy light. This can be performed with a wide array of fluorophores, each reacting to a different light wavelength, thereby potentially widening the scope of individual studies.

Here’s a video showing the new dyes fluorescing when triggered by visible light.

Some details about the achievement according to the study abstract:

Thiocarbonyl substitution within fluorophores results in significant loss of fluorescence via a photoinduced electron transfer-quenching mechanism as suggested by theoretical calculations. Significantly, upon exposure to air and visible light residing in their absorption regime (365–630 nm), thio-caged fluorophores can be efficiently desulfurized to their oxo derivatives, thus restoring strong emission of the fluorophores. The effective photoactivation makes thio-caged fluorophores promising candidates for super-resolution imaging, which was realized by photoactivated localization microscopy (PALM) with low-power activation light under physiological conditions in the absence of cytotoxic additives (e.g., thiols, oxygen scavengers), a feature superior to traditional PALM probes. The versatility of this thio-caging strategy was further demonstrated by multicolor super-resolution imaging of lipid droplets and proteins of interest.

Published study in Journal of the American Chemical Society: Single-Atom Fluorescence Switch: A General Approach toward Visible-Light-Activated Dyes for Biological Imaging

Via: Rice University