ONI’s Nanoimager powers small dyes breakthrough for toxicity-free live-cell super-resolution imaging

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SAN DIEGO, CA and OXFORD, UK, March 18, 2026

ONI’s Nanoimager powers small dyes breakthrough for toxicity-free live-cell super-resolution imaging

In a recent study by Nobel laureate Prof Stefan Hell’s team, ONI’s Nanoimager and its single-molecule technology was a key validation tool for the creation of far-red emitting (>680 nm) PaX dyes and their application using PhotoActivable Light Microscopy (PALM) for live-cell 2D and 3D super-resolution imaging. 

This new class of fluorophores solve a major problem in super-resolution microscopy: turn molecules “on” and “off” without harming living cells. Traditionally, scientists used bulky caging groups, making the dye toxic, less soluble, and prone to leaving harmful byproducts.

In this study published in Chem on February 2nd, Lincoln, Butkevich et al. from the Max Planck Institute for Medical Research in Heidelberg (Germany) reported caging- group-free, minimally sized PaX dyes (Photoactivatable Xanthones). These result in no byproducts and a much smaller molecular footprint. Importantly, far-red light is safer for live cells (low phototoxicity) and penetrates deeper into tissues. The study demonstrated their compatibility with HaloTag and SNAP-tag labeling, and their application in STED, MINFLUX, and PALM imaging.

Precisely, for the validation of PaX dyes in single-molecule PALM studies, the Hell lab used ONI’s Nanoimager microscope to capture the real-time activation of PaX dyes in live cells. The Nanoimager’s stability allowed for long exposures, while its 405 nm laser converted the dyes from their dark (off) state to their fluorescent (on) state. Leveraging the Nanoimager’s high-power lasers, TIRF illumination, and CMOS camera the team obtained images with sub-20 nm resolution.

“These dyes greatly simplify super-resolution microscopy workflows. Since they are compatible with living samples, and the common sample preparations, and microscopes, they enable high-quality imaging data with less efforts.” said Dr Richard Lincoln, one of the leading co-authors of the study.

Because these dyes are small and byproduct-free, scientists can label multiple cell structures simultaneously without interference. This makes them ideal for quantitative super-resolution microscopy applications, single-molecule tracking, and protein-protein interaction studies, with the potential to revolutionize drug discovery by visualizing drug-target interactions in real-time with unprecedented detail.

Read the article at: https://www.cell.com/chem/pdfExtended/S2451-9294(25)00457-7