Advances in highly doped upconversion nanoparticles

1Upconversion nanoparticles (UCNPs) are a unique class of optical nanomaterials doped with lanthanide ions featuring a wealth of electronic transitions within the 4f electron shells. These nanoparticles can up-convert two or more lower-energy photons into one high-energy photon–. Over the past decade, this unique anti-Stokes optical property has enabled a broad range of applications, spanning from background-free biological sensing and light-triggered drug delivery to solar energy harvesting and super-resolution microscopy–. To achieve high upconversion efficiency, it is essential to co-dope sensitizer ions alongside activator ions that have a closely matched intermediate-excited state–. This doping process requires a rational design that offers optimal interactions of a network of the sensitizer and activator ions, and the upconversion efficiency is highly dependent on the separating distance between the dopants. Therefore, the proper management of the doping concentration in a given nanoparticle will be the deciding factor in leveraging the energy transfer process and ultimately the luminescence performance of the nanoparticle–.

2In stark contrast to quantum dots, UCNPs contain individual and variable absorption and emission centres. Thus, the primary goal to increase the concentration of co-dopants in UCNPs is to directly improve their brightness. However, the constraint of concentration quenching that limits the amount of the dopants usable has been known for years in bulk materials (for example, Nd3+-doped YAG laser crystals), and tuning the luminescence properties has been largely hindered at relatively low-doping concentrations,. For nanomaterials with a high ratio of surface area to volume, high-doping concentration is likely to induce both cross-relaxation energy loss and energy migration to the surface quenchers. This, in turn, explains the much reduced luminescence quantum yield in upconversion nanomaterials relative to their bulk counterparts–. Encouragingly, over the past decade, a great deal of research efforts has been devoted to the study of the concentration quenching mechanisms,,,, thereby opening the door to many ground-breaking applications.

3In this review, we discuss the phenomenon and underlying mechanism of concentration quenching occurring in UCNPs, review the general and emerging strategies for overcoming the concentration quenching effect, and summarize the impact of highly doped UCNPs on a range of disruptive applications. In particular, we discuss the rational design of heterogeneously doped, multilayered UCNPs that allow us to precisely control the energy migration process and induce cross-relaxation between the dopants for unprecedented optical phenomena. We present the challenges and opportunities of the doping strategies in developing smaller and brighter nanoparticles as well as hybrid materials with synergetic multifunction.

4For a very long time, the problem of concentration quenching was the major obstacle that hindered the quest for highly luminescent materials,. The theory of concentration quenching in inorganic phosphors was introduced in 1954 by Dexter and Schulman, who pointed out that considerable quenching of luminescence in bulk materials arises when the activator concentration reaches 10−3–10−2 M[19]. Different mechanisms (resonance energy transfer, molecular interactions, and intermolecular photo-induced electron transfer) of concentration quenching in organic dyes have been studied since the early 1980s. The issue has limited the maximum number of fluorophores allowed in dye-doped silica nanoparticles. As a result, the detrimental effect of concentration quenching in luminescent materials imposes a restriction on access to a high level of luminescence intensity, in consequence hindering their further applications.

5The limitation set by the threshold of concentration quenching becomes a real problem for nanoscale luminescent materials (Figure 1a). As illustrated in Figure 1b, c, the general cause follows that high-doping concentration (shorter distance) leads to increased occurrence of energy transfer process between the dopants,. The excited-state electrons can be quickly short-circuited to the surface of nanomaterials, where a relatively large number of quenchers exist. Therefore, a dramatic decrease in luminescence intensity is observed. More specifically, the high-doping concentration facilitates both the energy migration of excited levels (typically within the sensitizer-sensitizer network) to the surface quenchers (Figure 1b),, and the inter-dopant (typically between activators) cross-relaxation that causes emission intensity loss each time, (Figure 1c).

6To avoid the quenching of luminescence, conventionally, the doping level has been kept relatively low to ensure a sizable separation between the dopants to prevent parasitic interaction. Accordingly, the critical distance (Förster critical distance) is typically in the range of 2−6 nm, meaning that the doping range should remain below 10−3 M for organic dye-doped SiO2 and 10−2 M for UCNPs (Box 1). For an efficient upconversion to proceed, the relatively low concentrations of sensitizers (typically around 20 mol %) and activators (below 2 mol %) are generally used in the hexagonal-phase alkaline rare-earth fluoride nanocrystal, β-AREF4, that is known as one of the most efficient host material for upconversion. Low-doping concentration is the key roadblock to yield smaller and brighter luminescent nanomaterials–, which requires a canonical approach to optimizing the composition and chemical architecture of nanoparticles as well as photoexcitation schemes,.

7The notorious photophysical phenomenon of concentration quenching is frequently observed in solutions containing a high concentration of organic dyes, typically in the range of 10−3–10−2 M,,,. The leading factors for concentration quenching involve Förster resonance energy transfer (FRET) and Dexter electron transfer (DET). FRET is based on classical dipole–dipole interactions between the transition dipoles of the donor (D) and acceptor (A). The rate of the energy transfer decreases with the D–A distance, R, falling off at a rate of 1/R6. DET is a short-range phenomenon that falls off exponentially with distance (proportional to e−kR, where k is a constant that depends on the inverse of the van der Waals radius of the atom) and depends on spatial overlap of donor and quencher molecular orbitals. The concentration quenching for phosphors is expressed by the rate constant, kCQ, determined from the equation for ηPL:

8where TPL is the intrinsic radiative decay time of the D, R is the distance between D–A and R0 is the Förster radius at which the energy transfer efficiency between D and A falls to 50%, ηet is the energy transfer efficiency, ηisc is the intersystem crossing efficiency, kph and knr are the rate constants of radiative and non-radiative decay, respectively.

9When this analogy extends to an inorganic system, such as UCNPs, the concentration quenching denotes the emission intensity decrease phenomenon as the dopant concentration is too high. Typically, the UCNPs contain two types of lanthanide dopants, that is, the sensitizer (D) and activator/emitter (A),. Though some singly doped (for example Er3+) particles can generate upconversion, researchers prefer to employ a sensitizer (for example Yb3+) to enlarge the absorbance in the NIR for enhanced upconversion luminescence. The process of the energy extraction from a sensitizer to an acceptor usually takes place via a non-radiative exchange (DET) or a multipolar interaction (FRET).

10Most of the lanthanides have plentiful excited states, which show a high possibility to couple with one another through multipolar interactions with matching energy gaps, known as cross-relaxation (Fig. 1c). But this kind of coupling effect only occurs when the doping concentration is above a certain threshold. Because the 4f–4f transitions are symmetry forbidden according to the Laporte selection rule, the consequences are low intensity and long-decay time,. This cross-relaxation is primarily responsible for concentration quenching because neighbour ions, one in the excited state and the other in the ground state, non-radiatively exchange energy generally followed by phonon relaxation. The cross-relaxation process is evidenced by shorter lifetimes and decreased luminescence intensity.

11Considering the energy transfer between two, or a network of, identical ions (for example, Yb3+ ions) in a concentrated system, the excited electrons will hop among the network. Such a process can quickly bring the excitation energy far away from the initial excited sensitizer, known as energy migration (Fig. 1b). In some specific systems, energy migration may be advantageous because it enables the upconversion from Eu3+ or Tb3+ emitters infused with an Gd3+ ion network, or for Nd3+-based sensitization with the assistance of an Yb3+ ion network. However, these systems would short-circuit the excitation energy to quenchers.

12Recently, great efforts have been made to overcome concentration quenching in luminescent nanoparticles, particularly from the upconversion research community. Various approaches have been developed to alleviate the threshold of concentration quenching in both homogeneously doped nanocrystals and heterogeneously doped core@shell nanocrystals. Box 2 summarizes four strategies that have proven effective for homogeneously doped nanocrystals. One of the most commonly used schemes is to passivate the particle’s surface with an inert shell (for example, NaYF4, NaGdF4, NaLuF4 or CaF2), which can block the pathway of energy migration to surface quenchers,,. The second strategy is to irradiate the particles with a high-energy flux that is sufficient for the activation of all dopant ions. The third strategy is to choose a host crystal featuring a large unit cell to keep the D–A distance large enough even for stoichiometric compositions,. And the last strategy is to improve the doping uniformity in the host nanomaterials,, which minimizes the segregation of ions and thus prevents local concentration quenching.

13Using wet-chemical synthesis methods developed over the past decade, it becomes possible to accurately control both the number and spatial distribution of dopants. This paves the way for a more efficient synthesis of heterogeneously doped core@multishell nanocrystals, which allows for the optimization of doping concentrations in each layer and selective isolation of different lanthanide ions to lower the probability of deleterious cross-relaxation. For example, Pilch et al. systematically studied a series of core@shell UCNPs to evaluate the effect of core@shell architecture on sensitizer and activator ions; by separating sensitizers and emitters through the use of multilayer core@shell nanostructures, the concentration quenching threshold of Er3+ was lifted from 2 to 5%.

14a Coating an inert shell: Inert shell passivation on a low-doping luminescent core is a common strategy to avoid surface quenching by shielding the luminescent core from surface quenchers. This strategy further helps highly doped UCNPs by preventing the migration of sensitized photon energy to the surface quenchers, providing a convenient solution for detrimental quenching effects,,,.

15b Increasing excitation power density: In the case of low irradiance, concentration quenching happens in highly doped UCNPs because too many nearby ground-state ions will easily take away the energy of excited-state ions. By supplying a high irradiance, either by using a high-power laser or focusing the excitation beam, a sufficient amount of excitation photon flux will be supplied to the large number of highly doped ions, and the majority of them will be at excited (intermediate) states, which reduces the number of detrimental ground-state ions. This strategy has proven highly effective in alleviating the thresholds of concentration quenching in UCNPs involving Tm3+ or Er3+ as emitters,. Benz et al. also described a rate equation model, which shows that the increased luminescence intensity for highly doped nanocrystals at a high irradiance is due to the enlarged distance between excited ions and ground-state ions.

16c Choosing a host nanocrystal with a large unit cell size,: The minimum distance between two dopants in a nanocrystal is determined by the size of the unit cell. Taking the β-NaYF4 crystalline structure as an example, the average distance between a sensitizer and an acceptor can be approximated using the following equation:, which is evolved from the known lattice parameters when ignoring the lattice distortion caused by doping. The parameters x and y represent the doping concentrations of the sensitizer and acceptor, respectively, while a and c are the lattice parameters of the hexagonal unit cells.

17d Improving the homogeneous distribution of dopants: A homogeneous distribution of dopants can avoid local concentration quenching. The layer-by-layer hot injection strategy is technically superior to conventional one-pot heating up synthesis procedures in achieving a high uniformity in the dopant distribution. Precise control on the Angstrom scale of the dopant distribution may be achieved by managing the rate of precursor injection.

18Building brighter nanocrystals: Highly doped homogeneous UCNPs displaying exceptional brightness were first reported by Zhao and coworkers. As shown in Figure 2a, an increase in the excitation irradiance from 1.6 × 104 to 2.5 × 106 W cm−2 enhances the overall luminescence intensity by a factor of 5.6, 71 and 1105 for 0.5, 4 and 8% Tm3+-doped nanocrystals, respectively. The high brightness of these Tm3+-doped UCNPs allows the tracking of single nanoparticles in living cells through an optical microscope. A similar trend was observed in highly Er3+-doped NaYF4:Yb3+ sub-10 nm nanocrystals (Figure 2b). As the excitation power increases, conventional UCNPs (2% Er3+) saturate in brightness while the highly doped UCNPs (20% Er3+) appear much brighter than the conventional UCNPs. The optimal concentration for Nd3+ (conventionally around 1%) was increased to 20% with the sensitization of indocyanine green (ICG), resulting in about a tenfold brightness enhancement (Figure 2c). Encouragingly, the upconversion emission from a series of NaYF4:x%Er3+@NaLuF4 nanocrystals clearly showed high brightness at high-doping concentrations of Er3+, with NaErF4@NaLuF4 (100% doping) being the brightest (Fig. 2d).

19The optimal concentration of Yb3+ sensitizer ions has also been pushed to its limit. Chen et al. reported that highly Yb3+-doped sub-10 nm cubic phase (α-) NaYF4:Yb3+,Tm3+ nanocrystals display a 43 times emission enhancement at NIR wavelengths compared to the conventional 20% Yb3+-doped one. With an inert shell coating, the α-NaYbF4:2%Er3+@CaF2 UCNPs display a 15-fold enhancement in visible light emission (Figure 2e). Using an inert CaF2 shell, heavy doping of Yb3+ ions in the ultra-small α-NaYF4:Yb3+,Tm3+ and α-NaYbF4:Tb3+ nanoparticles was found to dramatically enhance the upconversion emission for high-contrast bioimaging–. With a NaYF4 inert shell, the optimal concentration of Yb3+ sensitizer ions was quantitatively examined by characterizing β-phase UCNPs at the single-particle level.

20Emerging applications: With exceptional brightness and associated optical properties, a range of applications have emerged. For example, highly Tm3+-doped UCNPs enable single nanoparticle sensitivity using a suspended-core microstructured optical-fibre dip sensor (Fig. 2f),. The diverging brightness trends enable the optical encoding application by varying the excitation intensities. More recently, Li et al. employed living yeast as a natural bio-microlens to concentrate the excitation energy of light and to enhance upconversion luminescence, suggesting a new way of detection of cells.

21High efficiency of upconversion emission from the NIR to the UV was achieved by high Yb3+ doping in NaGdF4:70%Yb3+,1%Tm3+@NaGdF4 nanostructures, and by varying the NIR excitation power density the reversible dynamic red, green and blue reflections of superstructure in a single thin film was demonstrated (Figure 2g). Through confined energy migration, an efficient five-photon upconverted UV emission of Tm3+ has been demonstrated in a NaYbF4 host without concentration quenching, and the large amount of spontaneous upconversion emission provides sufficient gain in a micron-sized cavity to generate stimulated lasing emissions in deep-ultraviolet (around 311 nm) wavelength (Figure 2h).

22Using an increased excitation power density and highly Er3+-doped NaYF4:20%Yb3+,20%Er3+@NaYF4 UCNP, Drees et al. reported that resonance energy transfer has been enhanced by more than two orders of magnitude compared to that of standard NaYF4:20%Yb3+,2%Er3+@NaYF4 particles being excited at a low-power density. After conjugation with anti-GFP nanobodies, the formed UCNP nanoprobe was used to target GFP fusion proteins inside living cells via a blue upconversion luminescence-induced resonance energy transfer process (Figure 2i). More recently, Pliss et al. reported that NaYbF4:0.5%Tm3+@NaYF4 UCNPs emit six times higher blue emission, compared to typical NaYF4:30%Yb3+,0.5%Tm3+@NaYF4 UCNPs, for effective optogenetic activation using NIR light (Figure 2j).

23The precision in controlled growth has resulted in a library of intentional heterogeneously doped core@shell UCNPs,. The doping concentrations in multilayers of nanostructure can be optimized to satisfy the requirements of a particular application, for example, according to either excitation conditions,,, and/or desirable emission wavelengths,,, to produce a high-performance energy-migration-mediated upconversion process (Figure 3) or efficient light-to-heat conversion.

24Controlled energy migration: As shown in Figure 3a, the fine-tuning of upconversion emission colours through energy migration has been first demonstrated using a Gd3+ sublattice structure as an efficient energy transfer bridge across the core@shell interface. As shown in Figure 3b, upconversion emission with tunable wavelengths and lifetimes has been realized via a prescribed energy cascade of Yb3+ → Tm3+ → Gd3+ → lanthanide activators (for example, Tb3+, Eu3+, Dy3+ and Sm3+). Note that the efficiency of energy-migration-mediated upconversion emission of Tb3+, Eu3+ or Dy3+ at high-doping concentrations is more than two orders of magnitude of that from a Yb3+-sensitized cooperative energy transfer system. Efficient photon upconversion has also been demonstrated through the heterogeneous core@shell nanostructure of NaYbF4:Gd3+,Tm3+@NaGdF4@CaF2:Ce3+ with a high-doping concentration of Ce3+ in the shell layer. A CaF2 host has been employed to reduce the 4f–5d excitation frequency of Ce3+ to match the energy level of Gd3+. Zhang et al. have fabricated NaGdF4:Yb3+,Tm3+,Er3+@NaGdF4:Eu3+@NaYF4 incorporated with RGB-emitting lanthanide ions at high concentration, and generated high-brightness white light across the whole visible spectrum. Notably, apart from the lanthanide ions, organic dyes tethered on the surface of NaGdF4:Yb3+,Tm3+@NaGdF4 nanocrystals can accept the sensitized UV energy through the Gd3+-mediated energy transfer, which can dramatically improve the sensitivity in FRET-limited measurements. Apart from Gd3+ as the energy mediation ions, due to a large energy gap (ΔE > 5 hν) between respective levels,, Mn2+ and Tb3+ ions also show a similar function for energy migration from the core to shell when doped by high concentration of activators.

25Exciting UCNPs at 980 nm, through the transparent biological window (650–1350 nm), offers higher photo-biocompatibility and allows deeper tissue penetration than that achievable at 532 nm, as living cells can withstand around 3000 times more intensity at 980 nm than at 532 nm visible excitation. Considering the fact that water absorbs around 20 times more excitation light at 980 nm than at 800 nm, researchers have further designed core@shell UCNPs by shifting the excitation wavelength to around 800 nm. The key is to use Nd3+ ions as the sensitizer to absorb 800 nm photons. Because the absorption cross-section of Nd3+ ions at 800 nm is 25-fold larger than that of Yb3+ ions at 980 nm, Nd3+-doped UCNPs display brighter upconversion emissions and negligible overheating effects. Since homogeneously co-doping high concentration of Nd3+ ions and activators will quench the overall upconversion emission, owing to the deleterious back energy transfer from activators to Nd3+ ions, the doping concentration of Nd3+ has been limited to below 1%. To overcome this threshold, an energy migration system has been employed to separate Nd3+ ions and activators (Figure 3c). Yan et al. first demonstrated high-concentration doping of Nd3+ in core@shell UCNPs that displayed a much enhanced upconversion luminescence relative to those homogeneously doped (Figure 3d). Using these Nd3+-sensitized UCNPs, the authors further demonstrated superior imaging performance for in vivo imaging without the issue of tissue overheating (Figure 3d). However, further studies are still needed to investigate the penetration depth trade-off of using 800 nm excitation light, since the amount of light scattering increases in proportion to the fourth power of the frequency of the light. To this regard, a future research direction is to shift the excitation wavelength from the first NIR optical window (650–1000 nm) to the second NIR spectral window (1100–1350 nm), which is ideal for deep-tissue imaging because of reduced water absorption and light scattering.

26To optimize the doping concentration in core@shell structures, Xie et al. have found that the design of NaYF4:20%Yb3+,0.5%Tm3+,1%Nd3+@NaYF4:20%Nd3+ results in upconversion emission around seven times stronger than that of NaYF4:Nd3+,Yb3+,Tm3+@NaYF4. To further reduce the cross-relaxation and back energy transfer from activators to Nd3+ sensitizers, Zhong et al. reported a nanostructure design in the form of NaYF4:Yb3+,Er3+@NaYF4:Yb3+@NaNdF4:Yb3+, in which the intermediate NaYF4:Yb3+ shell separates Er3+ activators from Nd3+ primary sensitizers. With the doping concentration of Nd3+ being pushed to 90%, there is eight times more upconversion luminescence produced, compared to the NaYF4:Yb3+,Er3+@NaYF4:Nd3+ structure. Encouragingly, a more sophisticated doping pattern of NaYF4:2%Er3+,30%Yb3+@NaYF4:20%Yb3+@NaNdF4:10%Yb3+, with fine-tuning of Yb3+ concentrations at different layers, was found to facilitate more efficient energy transfer process of (Nd3+ → Yb3+) → (Yb3+) → (Yb3+ → Er3+) at higher Nd3+ doping concentration. This design further reduces the requirement in the excitation power, so that upconversion luminescence has been observed even under a 740 nm LED. A similar energy migration strategy has been proposed to get cooperative emission from Tb3+ ions, which demonstrated a tenfold upconversion enhancement under 800 nm photoexcitation of Nd3+ ions as compared to Yb3+ sensitization. The ratiometric Nd3+ → Yb3+ and Yb3+ → Er3+ energy transfer processes in the core@shell nanocrystals have also been used for temperature sensing in two different temperature ranges. More detailed and systematic studies of the concentrations of both the primary sensitizer and secondary sensitizers will improve the efficiency of energy cascade.

27Combining strategies presented above (Figure 3a, c), upconversion tuning with high-doping concentrations can be achieved by either Gd3+-mediated energy migration or Yb3+-mediated absorption/migration. For example, the core@multishell structure of NaYbF4:50%Nd3+@NaGdF4:Yb3+,Tm3+@NaGdF4:A (A: activator Eu3+, Tb3+, or Dy3+) has been utilized to initiate the energy migration from Gd3+ to the activators with high concentration. In this system, the Nd3+-sensitized UCNPs displayed emissions spanning from the UV to the visible region with high efficiency through a single wavelength excitation at 808 nm. More recently, Liu et al. designed a multilayer nanoparticle for simultaneously displaying short- and long-lived upconversion emission with high concentrations of different dopants at different layers, making multilevel anti-counterfeiting possible at a single-particle level.

28Blocking layer separation: In addition to the strategies of tuning excitation and emission properties, the control over doping location with a blocking layer (Figure 3e) has been demonstrated for orthogonal emissions,,, spectral/lifetime multiplexing, upconverting/downshifting, multimode imaging, and multi-optical functions in single particles. For example, reversible isomerization of spiropyran derivatives has been achieved by the orthogonal emissions of core@multishell UCNPs with a high-doping concentration of Nd3+ under irradiation at 800 and 980 nm (Figure 3f). A similar idea was used to efficiently trigger a reversible photocyclization of the chiral diarylethene molecular switch by the UV and visible luminescence from core@multishell UCNPs with dual wavelength NIR light transduction properties. The emission colours of these Ho3+/Tm3+ co-doped NaGdF4:Yb3+ UCNPs can be tuned by changing the laser power density or temperature, due to the different spectral responses. By design and synthesis of NaGdF4:Nd3+@NaYF4@NaGdF4:Nd3+,Yb3+,Er3+@NaYF4 nanoparticles, both upconversion and downshifting luminescence, sensitized by highly doped Nd3+, can be achieved without cross interference. Moreover, excited Nd3+ ions can transfer energy to other lanthanide ions and result in tunable downshifting emission. For instance, co-doping Yb3+ with Nd3+ at high concentrations would give an intense NIR emission centred around 980 nm due to the efficient energy transfer from Nd3+ to Yb3+. The spectral and lifetime characteristics can correlate orthogonally with excitation by constructing noninterfering luminescent regions in a nanoparticle, which enables the multiplexed fingerprint and time-gated luminescent imaging in both spectral and lifetime dimensions. More recently, Marciniak et al. have demonstrated the heterogeneous doping of Nd3+ ions with different concentrations in different parts of NaNdF4@NaYF4@NaYF4:1%Nd3+ nanoparticles to achieve three optical functions, namely efficient (η > 72%) light-to-heat conversion, bright NIR emission and relatively sensitive (SR > 0.1% K−1) localized temperature quantification. The undoped NaYF4 intermediate shell enables the separation of the 1% Nd3+-doped outer shell (for efficient Stokes emission) from 100% Nd3+-doped core (for cross-relaxation based efficient light-to-heat conversion).

29Cross-relaxation has often been perceived as being deleterious, but new research shows that cross-relaxation can render many unique properties, such as single-band emission,, energy looping, tunable colour/lifetime,, enhanced downshifting emissions and photo-avalanche effect for amplified-stimulated emission,.

30Single-band emission: High-throughput molecular profiling requires optical multiplexing of single-band emission probes to target multiple analytes without crosstalk (Figure 4b), but each lanthanide ion emitter in an UCNP has multiple energy levels with multiple emission peaks. Cross-relaxation by high-doping concentration has been used to quench the unwanted emission bands to yield single-band emission,. Chan et al. used combinatorial screening of multiple doped NaYF4 nanocrystals to identify a series of doubly and triply doped nanoparticles with pure emission spectra at various visible wavelengths. Approaching 100% red emission output has been reported by Wei et al. using highly doped activators, where the cross-relaxation effect dominates and quenches the green or blue emissions (Figure 4a). This strategy was successful in achieving pure red 696 or 660 nm upconversion emission as well as precisely tuning upconversion colours to study the underlying upconversion mechanisms.

31More recently, Chen et al. presented a new class of β-NaErF4:0.5%Tm3+@NaYF4 nanocrystals with bright red upconversion luminescence through high concentration Er3+-based host sensitization, in which Tm3+ ions are employed to trap excitation energy and to minimize the luminescence quenching effect. Introducing high concentrations of Ce3+ into NaYF4:Yb3+/Ho3+ or NaYF4:40%Gd3+ have greatly enhanced the red-to-green upconversion emission ratio of Ho3+ through effective cross-relaxation between Ce3+ and Ho3+,. Similarly, combining the strategy presented in Figure 3c, single-band red upconversion luminescence of Ho3+ has been achieved under 808 nm excitation from NaGdF4:Yb3+,Ho3+,Ce3+@NaYF4:Yb3+,Nd3+ core@shell nanoparticles with the shell layer highly doped with Nd3+ (around 10%). Also, doping a high concentration of Mn2+ into NaYF4:Yb3+,Er3+ nanocrystals has resulted in pure single-band red upconversion emission via an efficient energy transfer between Mn2+ and Er3+. Levy et al. used an energy-looping mechanism to non-resonantly excite upconversion in highly Tm3+-doped NaYF4:Tm3+ nanoparticles with 1064 nm light for deep-tissue imaging. In this work, as illustrated in Figure 4c, one Tm3+ ion can cross-relax by donating energy partially to a second Tm3+ ion in its ground state, resulting in two Tm3+ ions in their intermediate 3F4 state to enable efficient excited-state absorption at 1064 nm and emit 800 nm emissions.

32Full-colour/lifetime tuning: The energy transfer between the dopant ions in a core@shell nanostructure has also been found to be controllable by adjusting the pulse duration of the excitation laser (Figure 4d, e). By increasing the pulse duration from 0.2 to 6 ms (at 980 nm), the intensity ratio of green-to-red emission from the shell of NaYF4:Yb3+,Ho3+,Ce3+ with a high concentration of Ce3+ can be continuously modulated. The energy transfer from Ho3+ to Ce3+ by a cross-relaxation process 5I6(Ho3+) + 2F5/2(Ce3+) → 5I7(Ho3+) + 2F7/2(Ce3+) is only allowed under a long pulse excitation, while the transition from 5I6(Ho3+) to higher levels of 5F4, 5S2 prevails over the above cross-relaxation process involving Ce3+ by a short-pulse excitation. This judicious design has further generated pure blue upconversion emission by pumping at 800 nm by Nd3+ → Yb3+ → Tm3+ with a high concentration of Nd3+. Cross-relaxation has been employed for enhancing the downshifting emission between 1500 and 1700 nm for high-spatial resolution and deep-tissue penetration of photons for cerebral vascular image in the second NIR window. Facilitated by the high Ce3+-doping concentration, the Er3+ 4I13/2 level is significantly populated through the accelerated non-radiative relaxation of Er3+ 4I11/2 → 4I13/2 (Figure 4f), resulting in a ninefold enhancement of the downshifting 1550 nm luminescence of NaYbF4:2%Er3+,2%Ce3+@NaYF4 nanoparticles.

33Apart from colour tuning, luminescence decay lifetimes form another set of optical signatures,,,. Manipulating the degree of cross-relaxation by different Tm3+-doping concentrations can create a large range of lifetimes from 25.6 to 662.4 μs in the blue emission band, forming a library of lifetime-tunable τ-dots for optical multiplexing (Figure 4g),. Such an optical signature can be used as barcoding for security applications, and only a properly designed time-resolved detector can decode such a set of diverse time-domain optical barcodes. As demonstrated in Figure 4h, the ability to resolve superimposed lifetime-encoded images suggests a new way of optical data storage with high densities and fast data readout rates.

34Super-resolution imaging: Another intriguing example is nanoscopic imaging using highly Tm3+-doped UCNP as an effective stimulated emission depletion (STED) probe. The advent of super-resolution microscopy, such as STED fluorescence microscopy, has revolutionized biological fluorescence microscopy,, but STED requires extremely high-power laser densities and specialized fluorescent labels to achieve super-resolution imaging. Using the cross-relaxation effect, Liu et al. discovered a photon avalanche effect that facilitates the establishment of population inversion within a single highly Tm3+-doped UCNP (Figure 4i). This enables sub-30 nm optical super-resolution imaging with a STED beam density two orders of magnitude lower than that used on fluorescent dyes (Figure 4j). This effect has only been found in highly doped UCNPs because the cross-relaxation process, dominated at a high Tm3+-doping concentration, can trigger a photon avalanche to establish a population inversion between metastable and ground levels. In that respect, upon 808 nm beam depletion amplified-stimulated emission is realized, resulting in a higher-depletion efficiency and thus a reduced saturation intensity. Using this new mode of upconversion nanoscopy, Zhan et al. have reported super-resolution imaging of cell cytoskeleton with 11.8 nm NaGdF4:18%Yb3+,10%Tm3+ UCNPs (Figure 4k). Other schemes, based on Pr3+ or Er3+ doped UCNPs, have also been explored for super-resolution nanoscopic applications,

35One of the major challenges to transform upconversion nanotechnology into real-world applications is to enhance the brightness and emission efficiency of UCNPs. This review summarizes the advances in the development of highly doped UCNPs and emerging applications by overcoming the concentration quenching effect or smart exploitation of unique features of highly doped nanomaterials. Notably, the unique optical properties arising from the range of layer-by-layer heterogeneously doped nanoparticles have attracted immense scientific and technological interests. The intentional doping of high concentration of lanthanide ions into different sections across a single UCNP has been explored to enhance the desirable optical properties as well as introducing multifunctionality. Thus far, only spherical core@shell structures have been studied to modulate the energy transfer, while further investigations of heterogeneous one-dimension structures, such as rods, plates and dumbbells, are still needed,,. Controlled growth toward atomic precision is highly sought after for gaining a full understanding of the sophisticated energy transfer processes and for fine-tuning upconversion luminescence. For example, arranging high concentrations of dopants into a host nanocrystal along one direction could confine the direction of energy transfer, which may create new properties and enable novel applications going beyond the current isotropic 3D transfer processes.

36The unique optical properties of highly doped UCNPs discussed above have largely impacted biological and biomedical fields, such as single-molecule sensing, high-throughput multiplexed detection,, and super-resolution nanoscopy,. It is noteworthy that small-sized and bright UCNPs are indispensable to those applications. Owing to brightness issues, the majority of currently developed UCNPs are relatively large (around 20–50 nm). It has been challenging to design and fabricate highly doped sub-10 nm UCNPs with emission output comparable with that of quantum dots and organic dyes. To our delight, fine-tuning of the particle size below 10 nm was recently demonstrated for UCNP systems by homogeneous doping or at a high-doping concentrations. Nonetheless, the fabrication of sub-10 nm UCNPs with heterogeneously doped core@shell structures remains a formidable challenge.

37The surface molecules not only play an essential role in the controlled synthesis of nanomaterials, but they can also significantly alter the nanomaterial’s luminescence properties with new effects,. Examples include the recent developments of dye-sensitized UCNPs,,, and surface phonon enhanced UCNPs in a thermal field. Normally, lanthanide-doped inorganic nanocrystals exhibit narrowband (FWHM around 20 nm) and low (10−20 cm−2) absorption coefficients. It is notable that organic dyes have more than 10 times broader absorption spectra and 103–104-fold higher absorption cross-sections than Yb3+ sensitizer ions commonly used in UCNPs,,,. Therefore, despite photostability issues, the organic–inorganic hybrid nanomaterials (for example, dye-sensitized upconversion nanosystems) offer various possibilities. Utilizing the efficient energy transfer of cyanine derivatives anchored on the surface of NaYbF4:Tm3+@NaYF4:Nd3+ nanoparticles, Chen et al. demonstrated dye-sensitized upconversion. Upon 800 nm excitation, a sequential energy transfer, dye → Nd3+ → Yb3+ → activators, has enabled the dye-sensitized nanoparticles to emit around 25 times stronger than canonical NaYF4:Yb3+,Tm3+@NaYF4 nanoparticles excited at 980 nm. Similarly, the common triplet energy transfer could occur between inorganic nanocrystals and the surface dyes–. While thermal quenching broadly limits the luminescence efficiency at high temperatures in optical materials, Zhou et al. report that the phonons at the surface of highly Yb3+-doped UCNPs could combat thermal quenching and significantly enhance the upconversion brightness, particularly for sub-10 nm nanocrystals. We believe that these hybrid and heterogeneously doped nanomaterials have the potential in pushing the performance of UCNPs to a new level and imparting multifaceted photonic applications.