Persistent Luminescence Nanosensors: A Generalized Optode-Based Platform for Autofluorescence-Free Sensing in Biological Systems

Fluorescent nanosensors have revolutionized diagnostics and our ability to monitor cellular dynamics. Yet, distinguishing sensor signals from autofluorescence remains a challenge. Here, we merged optode-based sensing with near-infrared-emitting ZnGa2O4:Cr3+ persistent luminescence nanoparticles (PLNPs) to create nanocomposites for autofluorescence-free "glow-in-the-dark" sensing. Hydrophobic modification and incorporation of the persistent luminescence nanoparticles into an optode-based nanoparticle core yielded persistent luminescence nanosensors (PLNs) for five analytes (K+, Na+, Ca2+, pH, and O2) via two distinct mechanisms. We demonstrated the viability of the PLNs by quantifying K+ in fetal bovine serum, calibrating the pH PLNs in the same, and ratiometrically monitoring O2 metabolism in cultures of Saccharomyces cerevisiae, all the while overcoming their respective autofluorescence signatures. This highly modular platform allows for facile tuning of the sensing functionality, optical properties, and surface chemistry and promises high signal-to-noise ratios in complex optical environments.