Caging-group-free photoactivatable fluorescent dyes

New Materials

Ref.-No.: 0105-6260-BC

The invention introduces a groundbreaking technology comprising of caging-group-free photoactivatable fluorescent dyes. This innovative approach eliminates the need for conventional caging groups, offering small (500–600 Da), live-cell permeable and non-toxic markers, readily photoactivatable to bright and photostable fluorescent dyes suitable for a variety of applications, including conventional and super-resolution imaging methods, with a detection sensitivity down to a single molecule.


  • Caging-group-free activation: Reduces molecular complexity, simplifies chemical synthesis, and improves solubility and cell permeability.
  • Rapid and efficient photoactivation: Quantitative conversion to the fluorescent state with low UV (one photon) or NIR (two photon) light doses compatible with the complex cellular environment.
  • Enhanced photostability: Reduced photobleaching enables longer observation times and single-molecule-level sensitivity.
  • Live-cell labeling: Cell membrane permeability allows for rapid labeling with state- of the art technologies such as HaloTag, SNAP-tag, and bioorthogonal click chemistry.
  • No toxic or reactive byproducts: Ensures cell viability and integrity during long-term imaging processes.
  • Compatible with all microscopes: Suitable for a variety of conventional (confocal, wide-field) and super-resolution microscopy techniques, including PALM/STORM, STED and MINFLUX.
  • Additive-free imaging: No dedicated media/buffers enables detailed observation of cellular processes without compromising cell health.
  • Broad color options: Combinable yellow-green, orange, and red emission options with a single dedicated photoactivation wavelength.
  • Large Stokes shift option: Expands color-channel selection, facilitates multiplexing, and reduces spectral overlap.

Potential applications

  • Fluorescence microcopy and nanoscopy: Photoactivatable bright and photostable labels for live-cell labeling with protein tags, as organelle specific markers, and immunostaining, in conventional and super-resolution methods.
  • Biomedical research: Studying cellular processes, such as organelle or protein dynamics, and protein–protein interactions.
  • Pharmaceutical development: High-throughput imaging screening for drug discovery, target validation and pathway analysis.
  • Clinical diagnostic: Enhanced labelling for diagnostic probe and sensor development research.
  • Material science: Tracing and mapping of materials, surfaces and interfaces at the nanoscale, flow and diffusion studies.
  • Neuroscience: Observation of neuronal structure and activity with high precision.

Fig. 1: Photoactivatable xanthones (PaX) enable fluorescence imaging with several conventional and super-resolution microscopy techniques.


Traditional photoactivatable dyes rely on caging groups that add to the molecular mass of the fluorescent label, decrease solubility and can release toxic photoproducts. These new caging-group-free fluorescent labels have been designed with live-cell applications in mind. These labels provide an optimized tool for researchers, with significant improvements over prior art in terms of biocompatibility, efficiency, and imaging quality.


The technology leverages a novel photoactivation mechanism for a new class of photoactivatable xanthone-based dyes that can be precisely controlled by light without the need for traditional caging groups nor media additives. Upon irradiation, these dyes transition from a non-fluorescent to a bright and photostable fluorescent state, enabling high-resolution imaging of live cells. The dyes cover a wide spectrum of wavelengths and they are compatible with various labeling techniques and state of the art super-resolution microscopy methods.

Patent Information

PCT application (WO 2023284968 A1), entered the national phase in the USA and Europe


R. Lincoln et al., Nature Chemistry 2022, 14, 1013-1020. A general design of caging-group-free photoactivatable fluorophores for live-cell nanoscopy,

A. Aktalay et al., ACS Central Science 2023, 9, 1581-1590. Bioorthogonal caging-group-free photoactivatable probes for minimal-linkage-error nanoscopy,

Likhotkin et al., Journal of the American Chemical Society 2023, 145, 1530-1534. Photoactivatable large Stokes shift fluorophores for multicolor nanoscopy,

Remmel et al. Small Methods 2024, 2301497. Photoactivatable xanthone (PaX) dyes enable quantitative, dual color, and live-cell MINFLUX nanoscopy,

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