Energy-Transfer Editing in Lanthanide-Activated Upconversion Nanocrystals: A Toolbox for Emerging Applications

Abstract

Advanced nanoscale synthetic techniques provide a versatile platform for programmable control over the size, morphology, and composition of nanocrystals doped with lanthanide ions. Characteristic upconversion luminescence features originating from the 4f-4f optical transitions of lanthanides can be achieved through predesigned energy transfer pathways, enabling wide applications ranging from ultrasensitive biological detection to advanced spectroscopic instrumentation with high spatiotemporal resolution. Here, we review recent scientific and technological discoveries that have prompted the realization of these peculiar functions of lanthanide-doped upconversion nanocrystals and discuss the mechanistic studies of energy transfer involved in upconversion processes. These advanced schemes include cross relaxation-mediated depletion, multipulse sequential pumping, and nanostructural configuration design. Our emphasis is placed on disruptive technologies such as super-resolution microscopy, optogenetics, nanolasing, and optical anticounterfeiting, which take full advantage of the upconversion nanophenomena in relation to lanthanide-doped nanocrystals.

Figure 1

Representative scientific and technological breakthroughs through the development of functionalized upconversion nanocrystals.

Figure 2

Schematic illustration showing four major energy transfer pathways dominated in upconverting nanosystems. A list of chemical and physical approaches to energy transfer manipulation is included in the scheme.

Figure 3

(a) Schematic diagram of a simplified STED experimental setup. (b, c) A scheme showing the effective point spread function (PSF) achieved by overlaying the excitation beam with the donut-shaped depletion beam. (d) A scheme showing the decrease in the size of the effective PSF obtained by increasing the intensity of the depletion laser. (e) Emission spectra of NaYF₄:18%Yb/10%Tm nanoparticles upon different wavelength excitations. Note that 96% depletion efficiency of the 455 nm emission can be achieved by simultaneously implementing 980 nm CW excitation and 810 nm CW depletion. (f) Schematic sketch of net cross relaxation-mediated stimulated depletion (left) and net synergistic enhancement (right), typically observed from upconversion nanocrystals with high and low Tm³⁺ doping concentrations. (g, h) High resolution imaging, in multiphoton mode and STED mode, of cytoskeleton structures and desmin proteins in HeLa cancer cells. Panel d reproduced with permission from ref (58). Copyright 2013 Frontiers. Panels e–f reproduced with permission from ref (67). Copyright 2017 Nature.

Figure 4

Schematic illustration of the underlying mechanisms of optogenetic control through ChR2 protein over the opening/closing of ion channels in a cellular membrane. Ca²⁺ and Na⁺ can access the interior cell when ChR2 is activated upon 470 nm irradiation, resulting in membrane depolarization and neuronal signal firing. (a) The ion channel protein ChR2 is initially blocked in the dark. (b) ChR2 opens for cation transportation when excited by blue light. (c) Activation of the ChR2 channel through the use of upconversion nanoparticles upon 980 nm excitation.

Figure 5

Representative upconversion nanoparticle-associated optogenetics in vitro and in vivo. From left to right, cell, worm, fish, and mouse. Neuron cells. Top: Schematic illustration showing the use of polymer–nanocrystal hybrid scaffolds for neuron activation. Bottom: The magnified neuron–nanocrystal interface (left) and the repetitive potentials of a current–clamped hippocampal neuron evoked by 980 nm light irradiation (right). Caenorhabditis elegans. Top: Representative images showing the upconversion-mediated optogenetic reversal behavior of a worm with ChR2 expression in their mechanosensory neurons. Bottom: The correlation of the reversal response percentage with the concentration of the incubated upconversion nanocrystals (bottom left) and the recorded reversal response percentage under four types of experimental conditions. Zebrafish. In vivo photoluminescence imaging of zebrafish incubated with upconversion nanoparticles. Scale bar is 10 μm. Mouse. In vivo upconversion optogenetics. Top: X-ray and fluorescence images of the implanted micro-optrodes and the regions expressing ChR2 opsin. Bottom left: Schematic illustration showing transcranial NIR stimulation of the hippocampal engram for memory recall. Bottom right: Optical images of upconversion nanocrystals (blue) and EYFP-labeled ChR2 protein (green) in the dentate gyrus of a mouse. Panel Neuron cells reproduced with permission from ref (71). Copyright 2015 Royal Society of Chemistry. Panel C. elegans and panel Zebrafish reproduced with permission from refs ( and 75). Copyright 2016 and 2017 Wiley. Panel Mouse/Rat reproduced with permission from refs ( and 80). Copyright 2017 Elsevier Science and 2018 Science.

Figure 6

Upconversion nanocrystal-based lasing. (a) Multicolor pulse lasing spectra observed from a microcavity in a bottle-like geometry with a diameter (D) of 80 μm. The insets are images of the microcavity under different excitation powers. (b) Room-temperature deep-ultraviolet pulse lasing achieved through the use of a rationally designed microresonator. I: Plot of the intensity output versus the excitation power for a microresonator (D_m = 75 μm). The insets are the images of the microresonator with and without optical excitation. II: The lasing spectra of the microlaser at different excitation powers (D_m = 75 μm). (c) Room-temperature lasing spectra of three upconversion microrods (∼3 μm in radius) upon 980 nm excitation. The three small insets are the corresponding optical images, while the two large insets are the simulated optical field distribution within a microrod that emits at 654 nm and the optical image of a microrod (∼4 μm in radius) that emits white light lasing. (d) Continuous-wave lasing achieved by coupling energy-looping nanoparticles (ELNPs) to whispering-gallery modes of polystyrene microspheres. I: Schematic illustration showing the excitation and lasing occurring within the nanoparticle-coated microbeads. TIR stands for total internal reflection. II: Left: Wide-field image of the given lasing microbeads showing optical modes circulating within the resonator. Right: x–y plane projection of the simulated field distribution within a 5-μm polystyrene microsphere. Scale bar: 1 μm. III: Compiled emission spectra of the nanoparticles and the corresponding particle-coated beads, along with the simulated NIR spectra of whispering-gallery modes supported by a microsphere with a diameter of 5 μm. Panels a and c reproduced with permission from refs ( and 90). Copyright 2013 and 2017 American Chemical Society. Panels b and d reproduced with permission from refs ( and 91). Copyright 2016 and 2018 Nature.

Figure 7

Representative upconversion nanocrystal-associated anticounterfeiting at different levels of security. (a) Optical decoding of encrypted papers through NIR light exposure. (b) Top: Red–green–blue printing using nanoparticle-based inks. Bottom: Optical image of the as-printed QR code featuring multicolor emission. (c) Multicolor barcoding in a single microcrystal. Scale bar: 2 μm. (d) Multicolor barcoding through upconversion nanoparticle-encapsulated polymeric microparticles. Scale bar: 200 μm. (e–g) Anticounterfeiting based on color and excitation characteristics. (h) Color and phase angle optical encoding. (i) Lifetime-encoded anticounterfeiting. Note that different colors represent different lifetimes. (j) Multilevel anticounterfeiting through the use of nanoparticles with different colors, lifetimes and pumping conditions. (k) Multilevel anticounterfeiting through Mn²⁺-doped upconversion nanoparticles. Panels a, b, e, and h reproduced with permission from refs (, , , and 104). Copyright 2014, 2016, and 2017 Royal Society of Chemistry. Panels c, g, and j reproduced with permission from refs (, , and 106). Copyright 2014 and 2017 American Chemical Society. Panels d, f, i, and k reproduced with permission from refs (, , , and 107). Copyright 2014 and 2017 Nature.