Lanthanide-Based Nanosensors: Refining Nanoparticle Responsiveness for Single Particle Imaging of Stimuli

Abstract

Lanthanide nanoparticles (LNPs) are promising sensors of chemical, mechanical, and temperature changes; they combine the narrow-spectral emission and long-lived excited states of individual lanthanide ions with the high spatial resolution and controlled energy transfer of nanocrystalline architectures. Despite considerable progress in optimizing LNP brightness and responsiveness for dynamic sensing, detection of stimuli with a spatial resolution approaching that of individual nanoparticles remains an outstanding challenge. Here, we highlight the existing capabilities and outstanding challenges of LNP sensors, en-route to nanometer-scale, single particle sensor resolution. First, we summarize LNP sensor read-outs, including changes in emission wavelength, lifetime, intensity, and spectral ratiometric values that arise from modified energy transfer networks within nanoparticles. Then, we describe the origins of LNP sensor imprecision, including sensitivity to competing conditions, interparticle heterogeneities, such as the concentration and distribution of dopant ions, and measurement noise. Motivated by these sources of signal variance, we describe synthesis characterization feedback loops to inform and improve sensor precision, and introduce noise-equivalent sensitivity as a figure of merit of LNP sensors. Finally, we project the magnitudes of chemical and pressure stimulus resolution achievable with single LNPs at nanoscale resolution. Our perspective provides a roadmap for translating ensemble LNP sensing capabilities to the single particle level, enabling nanometerscale sensing in biology, medicine, and sustainability.

Reversibly Photoswitching Upconversion Nanoparticles for Super‐Sensitive Photoacoustic Molecular Imaging

“…When 3ThacacH was encapsulated in the nanoprobe, the UV emission intensity from the UCNPs decreased by 82.8 % at 345 nm and 80.2 % at 362 nm, and the lifetime of the UV emission of the UCNPs decreased from 336 to 308 μs at 345 nm and from 408 to 378 μs at 362 nm. These results show that the overall energy transfer efficiency from the UCNPs to 3ThacacH is high (>80 %), in which 7.3 % to 8.3 % is attributed to the nonradiative resonance energy transfer and the rest from the radiative photon reabsorption, as in the cases where UCNPs serve as “Nanolamps” [32] . It is worth noting that although even a thin inert shell can increase the distance between UCNP and 3ThacacH, thus significantly reduce the resonance energy transfer efficiency, [33] the 5 nm inert shell in our nanoprobe is essential for achieving strong UV emission from the UCNPs and preventing the strong water quenching effect in the aqueous phase.…”

“…UCNPs to 3ThacacH is high (> 80 %), in which 7.3 % to 8.3 % is attributed to the nonradiative resonance energy transfer and the rest from the radiative photon reabsorption, as in the cases where UCNPs serve as "Nanolamps". [32] It is worth noting that although even a thin inert shell can increase the distance between UCNP and 3ThacacH, thus significantly reduce the resonance energy transfer efficiency, [33] the 5 nm inert shell in our nanoprobe is essential for achieving strong UV emission from the UCNPs and preventing the strong water quenching effect in the aqueous phase.…”

Reversibly Photoswitching Upconversion Nanoparticles for Super‐Sensitive Photoacoustic Molecular Imaging

“…These results show that the overall energy transfer efficiency from the UCNPs to 3ThacacH is high (> 80 %), in which 7.3 % to 8.3 % is attributed to the nonradiative resonance energy transfer and the rest from the radiative photon reabsorption, as in the cases where UCNPs serve as "Nanolamps". [32] It is worth noting that although even a thin inert shell can increase the distance between UCNP and 3ThacacH, thus significantly reduce the resonance energy transfer efficiency, [33] the 5 nm inert shell in our nanoprobe is essential for achieving strong UV emission from the UCNPs and preventing the strong water quenching effect in the aqueous phase.…”

Responsive Sensors of Upconversion Nanoparticles

“…A thorough examination of sources of imprecision in sensing and remediation methods has been recently conducted by Casar et al Worth reiterating, there has been a call for platforms for establishing a structure–property relationship at the single-particle level, i.e. , not only with single-particle spectroscopy but also with advanced electron microscopy, for feedback-loop quality control of nanosensors. We also expect nanosensors to be scalable to interface with the different scales of biological systems (Figure C), biocompatible, and target specific and to overcome biological barriers (Figure D).…”