Fluorescent Probes for Copper Detection in Biological Systems

Copper ions play a pivotal role in enzymatic catalysis, redox homeostasis and neural function, yet dysregulation is implicated in neurodegenerative disorders, cardiovascular disease and metabolic syndromes. Fluorescent probes offer non-invasive, real-time monitoring of Cu⁺ and Cu²⁺ in complex biological milieus, combining high sensitivity, spatial resolution and temporal fidelity. Contemporary designs exploit mechanisms such as intramolecular charge transfer, excited‐state intramolecular proton transfer and spirolactam ring opening to achieve large fluorescence enhancements or quenching upon metal binding. Advances in ligand architecture, water solubility and membrane compatibility have yielded probes with sub-nanomolar detection limits, high selectivity over competing metal ions and minimal cytotoxicity. Ratiometric and lifetime‐based approaches enable quantitative imaging, while organelle-targeting motifs reveal copper distribution in lysosomes, mitochondria and the endoplasmic reticulum. Integration with fluorescence lifetime imaging microscopy further resolves dynamic copper pools in live cells. Collectively, these molecular tools are transforming our understanding of copper trafficking, signalling pathways and copper-dependent cell death, offering promising avenues for diagnostics, environmental monitoring and the study of copper-linked pathologies.

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Fluorescent Probes for Copper Detection in Biological Systems publication trend

The graph below shows the total number of articles in fluorescent probes for copper detection in biological systems across all publications each year (not limited to Nature Index journals).

Technical terms

Fluorescent probe: A molecule that emits light upon excitation and undergoes a measurable change in emission intensity or wavelength upon interaction with a target analyte.

Intramolecular charge transfer (ICT): A photophysical process in which electron density shifts from a donor to an acceptor moiety within a molecule, modulating fluorescence on analyte binding.

Excited-state intramolecular proton transfer (ESIPT): A mechanism where a proton moves within a molecule after excitation, yielding dual emission bands and enhanced sensitivity to environmental changes.

Fluorescence lifetime imaging microscopy (FLIM): An imaging technique that maps spatial variations in fluorescence decay times, allowing quantitative discrimination of probe states independent of intensity.

Stokes shift: The difference in wavelength between a fluorophore’s absorption and emission maxima, influencing contrast and detection sensitivity.

Limit of detection (LOD): The lowest analyte concentration that produces a signal distinguishable from background noise, typically defined at a specified confidence level.

References

1. Selective Detection of Cu+ Ions in Live Cells via Fluorescence Lifetime Imaging Microscopy. Angewandte Chemie International Edition (2021).
2. Rational design of a water-soluble, lipid-compatible fluorescent probe for Cu( i ) with sub-part-per-trillion sensitivity. Chemical Science (2016).
3. A Ratiometric Selective Fluorescent Probe Derived from Pyrene for Cu2+ Detection. Chemosensors (2022).
4. A highly selective and sensitive ICT-based Cu2+ fluorescent probe and its application in bioimaging. Ecotoxicology and Environmental Safety (2023).
5. Development of a Fluorescein-Based Probe with an “Off–On” Mechanism for Selective Detection of Copper (II) Ions and Its Application in Imaging of Living Cells. Biosensors (2023).
6. An ESIPT-Based Fluorescent Probe for Aqueous Cu+ Detection through Strip, Nanofiber and Living Cells. Molecules (2023).