Near infrared (NIR) excited lanthanide-doped upconversion nanoparticles (UCNPs) are emerging as a new type of fluorescent tag for biological applications, which can emit multi-photon ultraviolet, visible or NIR luminescence for imaging or activation of photosensitive molecules. Here, we present a comprehensive review on recent advances of UCNPs for a manifold of biological applications, including upconversion mechanisms, building bright multicolor upconversion nanocrystals, single nanoparticle and super resolution imaging, in vivo optical and multimodal imaging, photodynamic therapy, light-controlled drug release, biosensing, and toxicities. Our perspectives on the future development of UCNPs are also described.

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Single-nanoparticle-level sensing allows us to measure individual molecular interactions and probe environmental stimuli at nanometer-scale resolution. Despite these premises, limited success has been met hitherto due to the demanding challenge to distinguish a dimmed signal from a noisy background. Here, we describe an approach for high-sensitivity single-nanoparticle-level sensing of divalent copper (Cu 2+ ) ions through near-infrared-to-visible upconversion luminescence against a near-null background. This nanosensor utilizes ytterbium-(Yb 3+ ) and erbium (Er 3+ )-doped sodium yttrium fluoride (NaYF 4 ) upconversion nanoparticles (UCNPs) (maximal emission at 540 nm when excited at 980 nm) as an energy donor, of which the surface attaches Cu 2+ -dependent DNAzymes labeled with BHQ1 dye (Black Hole Quencher 1, maximal absorption at 548 nm) as energy acceptors. Adding a hint amount of Cu 2+ ions resulted in the cleavage of a BHQ1-containing moiety in DNAzymes, thus turning on upconversion luminescence for sensitive detection. Indeed, this approach allows us to perform single-nanoparticle-level detection of Cu 2+ ions with extraordinary signal-to-noise ratios (SNRs, >277) for all measured concentrations that cover 3 orders of magnitude (from sub-nM to μM). Importantly, a limit of detection of 220 pM was achieved, about sevenfold lower than the one at the ensemble level. Moreover, a stochastic particle-to-particle sensing behavior was also identified, featuring single-nanoparticle-level detection. This work untaps the usage of UCNPs for high-sensitivity single-nanoparticle-level biosensing.

A set of sub-15 nm ytterbium-enriched α-NaYbF4:Er3+@CaF2 core/shell upconversion nanoparticles have been developed for both ensemble- and single particle-level imaging studies, presenting a high quantum yield of 0.77% at a low saturation power density of 110 W cm−2.

Beam splitters are widely used in various optical systems, but traditional beam splitters are bulky and heavy, which are not conducive to the integrated utilization of optical devices. Metamaterials have attracted extensive attention as a kind of miniature artificial materials, and there have been many works on the design of metasurface beam splitters. Using metasurfaces, multiple functions of traditional beam splitters can be achieved. Meanwhile, metasurface beam splitters have the advantages of small size, easy integration, flexible design of beam-splitting performance, and tunable functions. This review surveys the current work on metasurface beam splitters and provides a classification and introduction to metasurface beam splitters. Metasurface beam splitters are expected to play a huge role in interferometers, multiplexing, multi-beam communications, and more.