Photon avalanche in lanthanide doped nanoparticles for biomedical applications: super-resolution imaging

Confocal fluorescence microscopy is a powerful tool for visualizing biological processes, but conventional laser scanning confocal microscopy cannot resolve structures below the diffraction limit of light. Although numerous sub-diffraction imaging techniques have been developed over the last decade, they are still limited by the photobleaching of fluorescent probes and by their complex instrumentation and alignment procedures. To address these issues, we propose a novel concept that relies on using photon avalanche (PA) anti-Stokes emission nanoparticles as luminescent labels. This technique leverages the highly non-linear relationship between photoluminescence intensity and excitation intensity observed with PA, which narrows the point spread function below 50 nm when the non-linearity exceeds 50. Using theoretical modelling, we evaluate the feasibility of obtaining PA in Nd³⁺ doped nanoparticles under non-resonant 1064 nm photoexcitation and study the impact of phenomenological parameters, such as photoexcitation intensity, concentration of dopants or features of the host matrix, on the theoretical PA behavior. Using these optimized parameters, our simulations resolved 20-nm features using non-linear orders of 80. These predictions require experimental proof of concept, which must be preceded by development of appropriate PA nanomaterials and experimental conditions to observe PA in nanoparticles at room temperature. When successful, the PA phenomenon in bio-functionalized nanoparticles shall radically simplify the technical means for super-resolution imaging.