Giant nonlinear optical responses from photon-avalanching nanoparticles.

Avalanche phenomena use steeply nonlinear dynamics to generate disproportionately large responses from small perturbations, and are found in a multitude of events and materials1. Photon avalanching enables technologies such as optical phase-conjugate imaging2, infrared quantum counting3 and efficient upconverted lasing4-6. However, the photon-avalanching mechanism underlying these optical applications has been observed only in bulk materials and aggregates6,7, limiting its utility and impact. Here we report the realization of photon avalanching at room temperature in single nanostructures-small, Tm3+-doped upconverting nanocrystals-and demonstrate their use in super-resolution imaging in near-infrared spectral windows of maximal biological transparency. Avalanching nanoparticles (ANPs) can be pumped by continuous-wave lasers, and exhibit all of the defining features of photon avalanching, including clear excitation-power thresholds, exceptionally long rise time at threshold, and a dominant excited-state absorption that is more than 10,000 times larger than ground-state absorption. Beyond the avalanching threshold, ANP emission scales nonlinearly with the 26th power of the pump intensity, owing to induced positive optical feedback in each nanocrystal. This enables the experimental realization of photon-avalanche single-beam super-resolution imaging7 with sub-70-nanometre spatial resolution, achieved by using only simple scanning confocal microscopy and without any computational analysis. Pairing their steep nonlinearity with existing super-resolution techniques and computational methods8-10, ANPs enable imaging with higher resolution and at excitation intensities about 100 times lower than other probes. The low photon-avalanching threshold and excellent photostability of ANPs also suggest their utility in a diverse array of applications, including sub-wavelength imaging7,11,12 and optical and environmental sensing13-15.

On the role of Gd3+ions in enhancement of UV emission from Yb3+-Tm3+up-converting LiYF4nanocrystals.

Materials capable of emitting ultraviolet (UV) radiation are sought for applications ranging from theranostics or photodynamic therapy to specific photocatalysis. The nanometer size of these materials, as well as excitation with near-infrared (NIR) light, is essential for many applications. Tetragonal tetrafluoride LiY(Gd)F4nanocrystalline host for up-converting Tm3+-Yb3+activator-sensitizer pair is a promising candidate to achieve UV-vis up-converted radiation under NIR excitation, important for numerous photo-chemical and bio-medical applications. Here, we provide insights into the structure, morphology, size and optical properties of up-converting LiYF4:25%Yb3+0.5%Tm3+colloidal nanocrystals, where 1, 5, 10, 20, 30 and 40% of Y3+ions were substituted with Gd3+ions. Low gadolinium dopant concentrations modify the size and up-conversion luminescence, while the Gd3+doping that is exceeding the structure resistance limit of the tetragonal LiYF4results in appearance of foreign phase and significant decrease of luminescence intensity. The intensity and kinetic behavior of Gd3+up-converted UV emission are also analyzed for various gadolinium ions concentrations. The obtained results form a background for further optimized materials and applications based on LiYF4nanocrystals.

Engineering the Compositional Architecture of Core-Shell Upconverting Lanthanide-Doped Nanoparticles for Optimal Luminescent Donor in Resonance Energy Transfer: The Effects of Energy Migration and Storage.

Förster Resonance Energy Transfer (FRET) between single molecule donor (D) and acceptor (A) is well understood from a fundamental perspective and is widely applied in biology, biotechnology, medical diagnostics, and bio-imaging. Lanthanide doped upconverting nanoparticles (UCNPs) have demonstrated their suitability as alternative donor species. Nevertheless, while they solve most disadvantageous features of organic donor molecules, such as photo-bleaching, spectral cross-excitation, and emission bleed-through, the fundamental understanding and practical realizations of bioassays with UCNP donors remain challenging. Among others, the interaction between many donor ions (in donor UCNP) and many acceptors anchored on the NP surface and the upconversion itself within UCNPs, complicate the decay-based analysis of D-A interaction. In this work, the assessment of designed virtual core-shell NP (VNP) models leads to the new designs of UCNPs, such as …@Er, Yb@Er, Yb@YbEr, which are experimentally evaluated as donor NPs and compared to the simulations. Moreover, the luminescence rise and decay kinetics in UCNP donors upon RET is discussed in newly proposed disparity measurements. The presented studies help to understand the role of energy-transfer and energy migration between lanthanide ion dopants and how the architecture of core-shell UCNPs affects their performance as FRET donors to organic acceptor dyes.

Laser Refrigeration by an Ytterbium-Doped NaYF4 Microspinner.

Thermal control of liquids with high (micrometric) spatial resolution is required for advanced research such as single molecule/cell studies (where temperature is a key factor) or for the development of advanced microfluidic devices (based on the creation of thermal gradients at the microscale). Local and remote heating of liquids is easily achieved by focusing a laser beam with wavelength adjusted to absorption bands of the liquid medium or of the embedded colloidal absorbers. The opposite effect, that is highly localized cooling, is much more difficult to achieve. It requires the use of a refrigerating micro-/nanoparticle which should overcome the intrinsic liquid heating. Remote monitoring of such localized cooling, typically of a few degrees, is even more challenging. In this work, a solution to both problems is provided. Remote cooling in D2 O is achieved via anti-Stokes emission by using an optically driven ytterbium-doped NaYF4 microparticle. Simultaneously, the magnitude of cooling is determined by mechanical thermometry based on the analysis of the spinning dynamics of the same NaYF4 microparticle. The angular deceleration of the NaYF4 particle, caused by the cooling-induced increase of medium viscosity, reveals liquid refrigeration by over -6 K below ambient conditions.

Single-Cell Biodetection by Upconverting Microspinners.

Near-infrared-light-mediated optical tweezing of individual upconverting particles has enabled all-optical single-cell studies, such as intracellular thermal sensing and minimally invasive cytoplasm investigations. Furthermore, the intrinsic optical birefringence of upconverting particles renders them light-driven luminescent spinners with a yet unexplored potential in biomedicine. In this work, the use of upconverting spinners is showcased for the accurate and specific detection of single-cell and single-bacteria attachment events, through real-time monitoring of the spinners rotation velocity of the spinner. The physical mechanisms linking single-attachment to the angular deceleration of upconverting spinners are discussed in detail. Concomitantly, the upconversion emission generated by the spinner is harnessed for simultaneous thermal sensing and thermal control during the attachment event. Results here included demonstrate the potential of upconverting particles for the development of fast, high-sensitivity, and cost-effective systems for single-cell biodetection.

Optical Forces at the Nanoscale: Size and Electrostatic Effects.

The reduced magnitude of the optical trapping forces exerted over sub-200 nm dielectric nanoparticles complicates their optical manipulation, hindering the development of techniques and studies based on it. Improvement of trapping capabilities for such tiny objects requires a deep understanding of the mechanisms beneath them. Traditionally, the optical forces acting on dielectric nanoparticles have been only correlated with their volume, and the size has been traditionally identified as a key parameter. However, the most recently published research results have shown that the electrostatic characteristics of a sub-100 nm dielectric particle could also play a significant role. Indeed, at present it is not clear what optical forces depend. In this work, we designed a set of experiments in order to elucidate the different mechanism and properties (i.e., size and/or electrostatic properties) that governs the magnitude of optical forces. The comparison between experimental data and numerical simulations have shown that the double layer induced at nanoparticle's surface, not considered in the classical description of nanoparticle's polarizability, plays a relevant role determining the magnitude of the optical forces. Here, the presented results constitute the first step toward the development of the dielectric nanoparticle over which enhanced optical forces could be exerted, enabling their optical manipulation for multiples purposes ranging from fundamental to applied studies.

Shaping Luminescent Properties of Yb3+ and Ho3+ Co-Doped Upconverting Core-Shell ß-NaYF4 Nanoparticles by Dopant Distribution and Spacing.

At the core of luminescence color and lifetime tuning of rare earth doped upconverting nanoparticles (UCNPs), is the understanding of the impact of the particle architecture for commonly used sensitizer (S) and activator (A) ions. In this respect, a series of core@shell NaYF4 UCNPs doped with Yb3+ and Ho3+ ions are presented here, where the same dopant concentrations are distributed in different particle architectures following the scheme: YbHo core and YbHo@…, …@YbHo, Yb@Ho, Ho@Yb, YbHo@Yb, and Yb@YbHo core-shell NPs. As revealed by quantitative steady-state and time-resolved luminescence studies, the relative spatial distribution of the A and S ions in the UCNPs and their protection from surface quenching has a critical impact on their luminescence characteristics. Although the increased amount of Yb3+ ions boosts UCNP performance by amplifying the absorption, the Yb3+ ions can also efficiently dissipate the energy stored in the material through energy migration to the surface, thereby reducing the overall energy transfer efficiency to the activator ions. The results provide yet another proof that UC phosphor chemistry combined with materials engineering through intentional core@shell structures may help to fine-tune the luminescence features of UCNPs for their specific future applications in biosensing, bioimaging, photovoltaics, and display technologies.

Upconverting nanoparticles: assessing the toxicity.

Lanthanide doped nanoparticles (Ln:NPs) hold promise as novel luminescent probes for numerous applications in nanobiophotonics. Despite excellent photostability, narrowband photoluminescence, efficient anti-Stokes emission and long luminescence lifetimes, which are needed to meet the requirements of multiplexed and background free detection at prolonged observation times, concern about their toxicity is still an issue for both in vivo and in vitro applications. Similar to other chemicals or pharmaceuticals, the very same properties that are desirable and potentially useful from a biomedical perspective can also give rise to unexpected and hazardous toxicities. In engineered bionanomaterials, the potentially harmful effects may originate not only from their chemical composition but also from their small size. The latter property enables the nanoparticles to bypass the biological barriers, thus allowing deep tissue penetration and the accumulation of the nanoparticles in a number of organs. In addition, nanoparticles are known to possess high surface chemical reactivity as well as a large surface-to-volume ratio, which may seriously affect their biocompatibility. Herein we survey the underlying mechanisms of nanotoxicity and provide an overview on the nanotoxicity of lanthanides and of upconverting nanoparticles.

All-Optical Data Processing with Photon-Avalanching Nanocrystalline Photonic Synapse.

Data processing and storage in electronic devices are typically performed as a sequence of elementary binary operations. Alternative approaches, such as neuromorphic or reservoir computing, are rapidly gaining interest where data processing is relatively slow, but can be performed in a more comprehensive way or massively in parallel, like in neuronal circuits. Here, time-domain all-optical information processing capabilities of photon-avalanching (PA) nanoparticles at room temperature are discovered. Demonstrated functionality resembles properties found in neuronal synapses, such as: paired-pulse facilitation and short-term internal memory, in situ plasticity, multiple inputs processing, and all-or-nothing threshold response. The PA-memory-like behavior shows capability of machine-learning-algorithm-free feature extraction and further recognition of 2D patterns with simple 2 input artificial neural network. Additionally, high nonlinearity of luminescence intensity in response to photoexcitation mimics and enhances spike-timing-dependent plasticity that is coherent in nature with the way a sound source is localized in animal neuronal circuits. Not only are yet unexplored fundamental properties of photon-avalanche luminescence kinetics studied, but this approach, combined with recent achievements in photonics, light confinement and guiding, promises all-optical data processing, control, adaptive responsivity, and storage on photonic chips.

Understanding Yb3+-sensitized photon avalanche in Pr3+ co-doped nanocrystals: modelling and optimization.

Among different upconversion processes where the emitted photon has higher energy than the one absorbed, photon avalanche (PA) is unique, because the luminescence intensity increases by 2-3 orders of magnitude in response to a tiny increase in excitation intensity. Since its discovery in 1979, PA has been observed in bulk materials but until recently, obtaining it at the nanoscale has been a significant challenge. In the present work, the PA phenomenon in ß-NaYF4 colloidal nanocrystals co-doped with Pr3+ and Yb3+ ions was successfully observed at 482 nm (3P0 → 3H4) and 607 nm (3P0 → 3H6) under excitation at 852 nm. The impact of Pr3+ ion concentration and pump power dependence on PA behavior was investigated, i.e. PA non-linearity slopes of luminescence intensity curves as a function of pump power density as well as PA thresholds. The highest slopes, namely 8.6 and 9.0, and the smallest thresholds equal to 286 kW cm-2 and 281 kW cm-2, observed for emission bands at 607 nm and 482 nm, respectively, were obtained for NaYF4:0.5%Pr3+,15%Yb3+@NaYF4 colloidal nanocrystals. Besides experimental research, simulations of PA behavior in Pr3+, Yb3+ co-doped materials were performed based on differential rate equations describing the phenomena that contribute to the existence of PA. The influence of different processes leading to PA, e.g. the rates of nonradiative and radiative transitions as well as energy transfers, on PA performance was simulated aiming to understand their roles in this complex sensitized system.

Lanthanide-doped heterostructured nanocomposites toward advanced optical anti-counterfeiting and information storage.

The continuously growing importance of information storage, transmission, and authentication impose many new demands and challenges for modern nano-photonic materials and information storage technologies, both in security and storage capacity. Recently, luminescent lanthanide-doped nanomaterials have drawn much attention in this field because of their photostability, multimodal/multicolor/narrowband emissions, and long luminescence lifetime. Here, we report a multimodal nanocomposite composed of lanthanide-doped upconverting nanoparticle and EuSe semiconductor, which was constructed by utilizing a cation exchange strategy. The nanocomposite can emit blue and white light under 365 and 394 nm excitation, respectively. Meanwhile, the nanocomposites show different colors under 980 nm laser excitation when the content of Tb3+ ions is changed in the upconversion nanoparticles. Moreover, the time-gating technology is used to filter the upconversion emission of a long lifetime from Tb3+ or Eu3+, and the possibilities for modulating the emission color of the nanocomposites are further expanded. Based on the advantage of multiple tunable luminescence, the nanocomposites are designed as optical modules to load optical information. This work enables multi-dimensional storage of information and provides new insights into the design and fabrication of next-generation storage materials.

Upconversion FRET quantitation: the role of donor photoexcitation mode and compositional architecture on the decay and intensity based responses.

Lanthanide-doped colloidal nanoparticles capable of photon upconversion (UC) offer long luminescence lifetimes, narrowband absorption and emission spectra, and efficient anti-Stokes emission. These features are highly advantageous for Förster Resonance Energy Transfer (FRET) based detection. Upconverting nanoparticles (UCNPs) as donors may solve the existing problems of molecular FRET systems, such as photobleaching and limitations in quantitative analysis, but these new labels also bring new challenges. Here we have studied the impact of the core-shell compositional architecture of upconverting nanoparticle donors and the mode of photoexcitation on the performance of UC-FRET from UCNPs to Rose Bengal (RB) molecular acceptor. We have quantitatively compared luminescence rise and decay kinetics of Er3+ emission using core-only NaYF4: 20% Yb, 2% Er and core-shell NaYF4: 20% Yb @ NaYF4: 20% Yb, 5% Er donor UCNPs under three photoexcitation schemes: (1) direct short-pulse photoexcitation of Er3+ at 520 nm; indirect photoexcitation of Er3+ through Yb3+ sensitizer with (2) 980 nm short (5-7 ns) or (3) 980 nm long (4 ms) laser pulses. The donor luminescence kinetics and steady-state emission spectra differed between the UCNP architectures and excitation schemes. Aiming for highly sensitive kinetic upconversion FRET-based biomolecular assays, the experimental results underline the complexity of the excitation and energy-migration mechanisms affecting the Er3+ donor responses and suggest ways to optimize the photoexcitation scheme and the architecture of the UCNPs used as luminescent donors.

Quantitative Comparison of the Light-to-Heat Conversion Efficiency in Nanomaterials Suitable for Photothermal Therapy.

Functional colloidal nanoparticles capable of converting between various energy types are finding an increasing number of applications. One of the relevant examples concerns light-to-heat-converting colloidal nanoparticles that may be useful for localized photothermal therapy of cancers. Unfortunately, quantitative comparison and ranking of nanoheaters are not straightforward as materials of different compositions and structures have different photophysical and chemical properties and may interact differently with the biological environment. In terms of photophysical properties, the most relevant information to rank these nanoheaters is the light-to-heat conversion efficiency, which, along with information on the absorption capacity of the material, can be used to directly compare materials. In this work, we evaluate the light-to-heat conversion properties of 17 different nanoheaters belonging to different groups (plasmonic, semiconductor, lanthanide-doped nanocrystals, carbon nanocrystals, and metal oxides). We conclude that the light-to-heat conversion efficiency alone is not meaningful enough as many materials have similar conversion efficiencies─in the range of 80-99%─while they significantly differ in their extinction coefficient. We therefore constructed their qualitative ranking based on the external conversion efficiency, which takes into account the conventionally defined light-to-heat conversion efficiency and its absorption capacity. This ranking demonstrated the differences between the samples more meaningfully. Among the studied systems, the top-ranking materials were black porous silicon and CuS nanocrystals. These results allow us to select the most favorable materials for photo-based theranostics and set a new standard in the characterization of nanoheaters.

Standardization of Methodology of Light-to-Heat Conversion Efficiency Determination for Colloidal Nanoheaters.

Localized photothermal therapy (PTT) has been demonstrated to be a promising method of combating cancer, that additionally synergistically enhances other treatment modalities such as photodynamic therapy or chemotherapy. PTT exploits nanoparticles (called nanoheaters), that upon proper biofunctionalization may target cancerous tissues, and under light stimulation may convert the energy of photons to heat, leading to local overheating and treatment of cancerous cells. Despite extensive work, there is, however, no agreement on how to accurately and quantitatively compare light-to-heat conversion efficiency (ηQ) and rank the nanoheating performances of various groups of nanomaterials. This disagreement is highly problematic because the obtained ηQ values, measured with various methods, differ significantly for similar nanomaterials. In this work, we experimentally review existing optical setups, methods, and physical models used to evaluate ηQ. In order to draw a binding conclusion, we cross-check and critically evaluate the same Au@SiO2 sample in various experimental conditions. This critical study let us additionally compare and understand the influence of the other experimental factors, such as stirring, data recording and analysis, and assumptions on the effective mass of the system, in order to determine ηQ in a most straightforward and reproducible way. Our goal is therefore to contribute to the understanding, standardization, and reliable evaluation of ηQ measurements, aiming to accurately rank various nanoheater platforms.

Enhancing FRET biosensing beyond 10 nm with photon avalanche nanoparticles.

Förster Resonance Energy Transfer (FRET) between donor (D) and acceptor (A) molecules is a phenomenon commonly exploited to study or visualize biological interactions at the molecular level. However, commonly used organic D and A molecules often suffer from photobleaching and spectral bleed-through, and their spectral properties hinder quantitative analysis. Lanthanide-doped upconverting nanoparticles (UCNPs) as alternative D species offer significant improvements in terms of photostability, spectral purity and background-free luminescence detection, but they bring new challenges related to multiple donor ions existing in a single large size UCNP and the need for nanoparticle biofunctionalization. Considering the relatively short Förster distance (typically below 5-7 nm), it becomes a non-trivial task to assure sufficiently strong D-A interaction, which translates directly to the sensitivity of such bio-sensors. In this work we propose a solution to these issues, which employs the photon avalanche (PA) phenomenon in lanthanide-doped materials. Using theoretical modelling, we predict that these PA systems would be highly susceptible to the presence of A and that the estimated sensitivity range extends to distances 2 to 4 times longer (i.e. 10-25 nm) than those typically found in conventional FRET systems. This promises high sensitivity, low background and spectral or temporal biosensing, and provides the basis for a radically novel approach to combine luminescence imaging and self-normalized bio-molecular interaction sensing.

Synergy between NIR luminescence and thermal emission toward highly sensitive NIR operating emissive thermometry.

There are many figures of merit, which determine suitability of luminescent thermometers for practical applications. These include thermal sensitivity, thermal accuracy as well as ease and cost effectivness of technical implementation. A novel contactless emission thermometer is proposed, which takes advantage of the coexistence of photoluminescence from Nd3+ doping ions and black body emission in transparent Nd3+ doped-oxyfluorotellurite glass host matrix. The opposite temperature dependent emission from these two phenomena, enables to achieve exceptionally high relative sensitivity SR = 8.2%/°C at 220 °C. This enables to develop new type of emissive noncontact temperature sensors.

Standardizing luminescence nanothermometry for biomedical applications.

Luminescence nanothermometry enables accurate, remote, and all-optically-based thermal sensing. Notwithstanding its fast development, there are serious obstacles hindering reproducibility and reliable quantitative assessment of nanothermometers, which impede the intentional design, optimization and use of these sensors. These issues include ambiguities or absence of established universal rules for quantitative evaluation, incorrect assumptions about the mechanisms behind the thermal response of the sensors as well as the dependence of the nanothermometers readout on external conditions and host materials themselves. In this perspective article, we discuss these problems and propose a series of standardization guidelines to be followed. This critical discourse constitutes the first required step towards the ubiquitous acceptance, by the scientific community, of luminescence thermometry as a reliable tool for remote temperature determination in numerous practical biomedical implementations.

Heterodimers made of metal-organic frameworks and upconversion nanoparticles for bioimaging and pH-responsive dual-drug delivery.

Developing multifunctional nanocomposites for a pH-responsive controlled dual-drug delivery is still a huge challenge. Herein, we report a gentle and simple method for growing metal-organic frameworks (MOFs) that can load two anticancer drugs, namely DOX and 5-FU (doxorubicin and 5-fluorouracil), on the surface of upconversion nanoparticles (UCNPs) by the reactions of Schiff bases and electrostatic adsorption. The resulting pH-responsive UCMOFs@D@5 nanosystem showed effective dual-drug release by the cleavage of chemical bonds and the disruption of the MOF structure under acidic conditions. Moreover, the final nanosystem UCMOFs@D@5 showed much higher cytotoxicity in comparison with UCMOFs@D and UCMOFs@5, which loaded only one kind of drug, respectively, after being incubated with human cervical cancer (HeLa) cells, indicating that Dox and 5-FU released from the final nanosystem had synergistic effects on cytotoxicity. Cellular uptake studies showed that UCMOFs@D@5 was well uptaken by HeLa cells and has potential for bioimaging applications in intracellular fluorescence imaging with high-contrast, and is beneficial for the intracellular localization of anti-cancer drugs. In addition, the nanosystem can be successfully applied in T1-weighted magnetic resonance imaging. Therefore, we developed a visualized tracking agent combined with MOFs to load two anticancer drugs to form a nanosystem for diagnosis and synergistic treatment, thus achieving the bioimaging and stimulation-responsive dual-drug release.

Spectral properties of Tm3+ doped NaYF4 up-converting nanoparticles under single and double photoexcitation wavelengths.

As soon as excited long-living levels of lanthanides become populated, numerous novel photoexcitation schemes may become available. It paves the way to numerous new possibilities or applications, such as up-conversion (UC) enhancement or intentional depletion towards stimulated emission depletion microscopy (STED). However, this type of studies requires the possibility of performing power dependent measurements upon both single and double photoexcitation. In this article a newly developed setup for double photoexcitation is presented together with preliminary data of Tm3+ doped NaYF4 nanoparticles with different composition and concentration. The results demonstrate different susceptibility of Tm3+ luminescence to numerous factors, such as chemical architecture (composition and design) of the nanoparticles as well as relative photoexcitation intensity at different wavelengths (∼800 nm and 1064 nm).