Three-photon imaging using defect-induced photoluminescence in biocompatible ZnO nanoparticles

Although optical spectroscopy promises improved lateral resolution for cancer imaging, its clinical use is seriously impeded by background fluorescence and photon attenuation even in the so-called two-photon absorption (2PA) imaging modality. An efficient strategy to meet the clinical cancer imaging needs, beyond what two-photon absorption (2PA) offers, is to use longer excitation wavelengths outside the water absorption window (~950-1300 nm) through three-photon absorption (3PA). A variety of fluorescent dyes and nanoparticles (NPs) have been used in 3PA imaging. However, their non-linear 3PA coefficient is often low necessitating high excitation powers, which cause overheating, photodamage, and photo-induced toxicity. To address this demand we designed defected ZnO nanoparticles (ZnO NPs) for enabling a low-power 3PA paradigm at longer excitation and emission wavelengths, lower background noise, and improved spatial resolution (<1 um) at powers below 5 mW.