Upconverting nanoparticles provide valuable benefits as optical probes for bioimaging and Förster resonant energy transfer (FRET) due to their high signal-to-noise ratio, photostability, and biocompatibility; yet making nanoparticles small yields a significant decay in brightness due to increased surface quenching. Approaches to improve the brightness of UCNPs exist but often require increased nanoparticle size. Here we present a unique core-shell-shell nanoparticle architecture for small (sub-20 nm), bright upconversion with several key features: 1) maximal sensitizer concentration in the core for high near-infrared absorption, 2) efficient energy transfer between core and interior shell for strong emission, and 3) emitter localization near the nanoparticle surface for efficient FRET. This architecture consists of β-NaYbF 4 (core) @NaY 0.8−x Er x Gd 0.2 F 4 (interior shell) @NaY 0.8 Gd 0.2 F 4 (exterior shell), where sensitizer and emitter ions are partitioned into core and interior shell, respectively. Emitter concentration is varied (x = 1, 2, 5, 10, 20, 50, and 80%) to investigate influence on single particle brightness, upconversion quantum yield, decay lifetimes, and FRET coupling. We compare these seven samples with the field-standard core-shell architecture of β-NaY 0.58 Gd 0.2 Yb 0.2 Er 0.02 F 4 (core) @NaY 0.8 Gd 0.2 F 4 (shell), with sensitizer and emitter ions codoped in the core. At a single particle level, the core-shell-shell design was up to 2-fold brighter than the standard core-shell design. Further, by coupling a fluorescent dye to the surface of the two different architectures, we demonstrated up to 8-fold improved emission enhancement with the core-shell-shell compared to the core-shell design. We show how, given proper consideration for emitter concentration, we can design a unique nanoparticle architecture to yield comparable or improved brightness and FRET coupling within a small volume.

Lanthanide-doped nanoparticles are an emerging class of optical sensors, exhibiting sharp emission peaks, high signal-to-noise ratio, photostability, and a ratiometric color response to stress. The same centrosymmetric crystal field environment that allows for high mechanosensitivity in the cubic-phase (α), however, contributes to low upconversion quantum yield (UCQY). In this work, we engineer brighter mechanosensitive upconverters using a core-shell geometry. Sub-25 nm α-NaYF:Yb,Er cores are shelled with an optically inert surface passivation layer of ∼4.5 nm thickness. Using different shell materials, including NaGdF, NaYF, and NaLuF, we study how compressive to tensile strain influences the nanoparticles' imaging and sensing properties. All core-shell nanoparticles exhibit enhanced UCQY, up to 0.14% at 150 W/cm, which rivals the efficiency of unshelled hexagonal-phase (β) nanoparticles. Additionally, strain at the core-shell interface can tune mechanosensitivity. In particular, the compressive Gd shell results in the largest color response from yellow-green to orange or, quantitatively, a change in the red to green ratio of 12.2 ± 1.2% per GPa. For all samples, the ratiometric readouts are consistent over three pressure cycles from ambient to 5 GPa. Therefore, heteroepitaxial shelling significantly improves signal brightness without compromising the core's mechano-sensing capabilities and further, promotes core-shell cubic-phase nanoparticles as upcoming in vivo and in situ optical sensors.

We demonstrate a facile method to improve upconversion quantum yields in Yb,Er-based nanoparticles via emission dye-sensitization. Using the commercially available dye ATTO 542, chosen for its high radiative rate and significant spectral overlap with the green emission of Er, we decorate the surfaces of sub-25 nm hexagonal-phase Na(Y/Gd/Lu)F:YbEr upconverting nanoparticles with varying dye concentrations. Upconversion photoluminescence and absorption spectroscopy provide experimental confirmation of energy transfer to and emission from the dye molecules. Upconversion quantum yield is observed to increase with dye sensitization, with the highest enhancement measured for the smallest particles investigated (10.9 nm in diameter); specifically, these dye-decorated particles are more than 2× brighter than are unmodified, organic-soluble nanoparticles and more than 10× brighter than are water-soluble nanoparticles. We also observe 3× lifetime reductions with dye adsorption, confirming the quantum yield enhancement to result from the high radiative rate of the dye. The approach detailed in this work is widely implementable, renders the nanoparticles water-soluble, and most significantly improves sub-15 nm nanoparticles, making our method especially attractive for biological imaging applications.

The optical efficiency of lanthanide-based upconversion is intricately related to the crystalline host lattice. Different crystal fields interacting with the electron clouds of the lanthanides can significantly affect transition probabilities between the energy levels. Here, we investigate six distinct alkaline-earth rare-earth fluoride host materials (M1-xLnxF2+x, MLnF) for infrared-to-visible upconversion, focusing on nanoparticles of CaYF, CaLuF, SrYF, SrLuF, BaYF, and BaLuF doped with Yb3+ and Er3+. We first synthesize ~5 nm upconverting cores of each material via a thermal decomposition method. Then we introduce a dropwise hot-injection method to grow optically inert MYF shell layers around the active cores. Five distinct shell thicknesses are considered for each host material, resulting in 36 unique, monodisperse upconverting nanomaterials each with size below ~15nm. The upconversion quantum yield (UCQY) is measured for all core/shell nanoparticles as function of shell thickness and compared with hexagonal (β-phase) NaGdF4, a traditional upconverting host lattice. While the UCQY of core nanoparticles is below the detection limit (<10−5%), it increases by four to five orders of magnitude as the shell thickness approaches 4–6 nm. The UCQY values of our cubic MLnF nanoparticles meet or exceed the β-NaGdF4 reference sample. Across all core/shell samples, SrLuF nanoparticles are the most efficient, with UCQY values of 0.53% at 80 W/cm2 for cubic nanoparticles with ~11 nm edge length. This efficiency is 5 times higher than our β-NaGdF4 reference material with comparable core size and shell thickness. Our work demonstrates efficient and bright upconversion in ultra-small alkaline-earth-based nanoparticles, with applications spanning biological imaging and optical sensing.

Electron microscopy (EM) has been instrumental in our understanding of complex biological systems. Although EM reveals cellular morphology with nanoscale resolution, it does not provide information on the location of different types of proteins. An EM-based bioimaging technology capable of localizing individual proteins and resolving protein-protein interactions with respect to cellular ultrastructure would provide important insights into the molecular biology of a cell. Here, we synthesized small lanthanide-doped nanoparticles, and measured the absolute photon emission rate of individual nanoparticles resulting from a given electron excitation flux (cathodoluminescence). Our results suggest that the optimization of nanoparticle composition, synthesis protocols and electron imaging conditions can lead to sub-20-nm nano-labels that would enable high signal-to-noise localization of individual biomolecules within a cellular context. In ensemble measurements, these labels exhibit narrow spectra of nine distinct colors, so that the imaging of biomolecules in a multicolor EM modality may be possible.

Thin films with tunable and homogeneous composition are required for many applications. We report the synthesis and characterization of a new class of compositionally homogeneous thin films that are amorphous solid solutions of AlO and transition metal oxides (TMO) including VO, CrO, MnO, FeO, CoO, NiO, CuO, and ZnO. The synthesis is enabled by the rapid decomposition of molecular transition-metal nitrates TM(NO) at low temperature along with precondensed oligomeric Al(OH)(NO) cluster species, both of which can be processed from aq solution. The films are dense, ultrasmooth (R < 1 nm, near 0.1 nm in many cases), and atomically mixed amorphous metal-oxide alloys over a large composition range. We assess the chemical principles that favor the formation of amorphous homogeneous films over rougher phase-segregated nanocrystalline films. The synthesis is easily extended to other compositions of transition and main-group metal oxides. To demonstrate versatility, we synthesized amorphous VCrMnFeZnAlO and VCrFeAlO with R ≈ 0.1 nm and uniform composition. The combination of ideal physical properties (dense, smooth, uniform) and broad composition tunability provides a platform for film synthesis that can be used to study fundamental phenomena when the effects of transition metal cation identity, solid-state concentration of d-electrons or d-states, and/or crystallinity need to be controlled. The new platform has broad potential use in controlling interfacial phenomena such as electron transfer in solar-cell contacts or surface reactivity in heterogeneous catalysis.

Upconverting nanoparticles (UCNPs) are promising tools for background-free imaging and sensing. However, their usefulness for in vivo applications depends on their biocompatibility, which we define by their optical performance in biological environments and their toxicity in living organisms. For UCNPs with a ratiometric color response to mechanical stress, consistent emission intensity and color are desired for the particles under nonmechanical stimuli. Here, we test the biocompatibility and mechanosensitivity of α-NaYF 4 :Yb,Er@NaLuF 4 nanoparticles. First, we ligand-strip these particles to render them dispersible in aqueous media. Then, we characterize their mechanosensitivity (∼30% in the red-to-green spectral ratio per GPa), which is nearly 3-fold greater than those coated in oleic acid. We next design a suite of ex vivo and in vivo tests to investigate their structural and optical properties under several biorelevant conditions: over time in various buffers types, as a function of pH, and in vivo along the digestive tract of Caenorhabditis elegans worms. Finally, to ensure that the particles do not perturb biological function in C. elegans , we assess the chronic toxicity of nanoparticle ingestion using a reproductive brood assay. In these ways, we determine that mechanosensitive UCNPs are biocompatible, i.e., optically robust and nontoxic, for use as in vivo sensors to study animal digestion.

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.