Ion-induced bias in Ag2S luminescent nanothermometers.

Luminescence nanothermometry allows measuring temperature remotely and in a minimally invasive way by using the luminescence signal provided by nanosized materials. This technology has allowed, for example, the determination of intracellular temperature and in vivo monitoring of thermal processes in animal models. However, in the biomedical context, this sensing technology is crippled by the presence of bias (cross-sensitivity) that reduces the reliability of the thermal readout. Bias occurs when the impact of environmental conditions different from temperature also modifies the luminescence of the nanothermometers. Several sources that cause loss of reliability have been identified, mostly related to spectral distortions due to interaction between photons and biological tissues. In this work, we unveil an unexpected source of bias induced by metal ions. Specifically, we demonstrate that the reliability of Ag2S nanothermometers is compromised during the monitoring of photothermal processes produced by iron oxide nanoparticles. The observed bias occurs due to the heat-induced release of iron ions, which interact with the surface of the Ag2S nanothermometers, enhancing their emission. The results herein reported raise a warning to the community working on luminescence nanothermometry, since they reveal that the possible sources of bias in complex biological environments, rich in molecules and ions, are more numerous than previously expected.

Exploring the Origin of the Thermal Sensitivity of Near-Infrared-II Emitting Rare Earth Nanoparticles.

Rare-earth doped nanoparticles (RENPs) are attracting increasing interest in materials science due to their optical, magnetic, and chemical properties. RENPs can emit and absorb radiation in the second biological window (NIR-II, 1000-1400 nm) making them ideal optical probes for photoluminescence (PL) in vivo imaging. Their narrow emission bands and long PL lifetimes enable autofluorescence-free multiplexed imaging. Furthermore, the strong temperature dependence of the PL properties of some of these RENPs makes remote thermal imaging possible. This is the case of neodymium and ytterbium co-doped NPs that have been used as thermal reporters for in vivo diagnosis of, for instance, inflammatory processes. However, the lack of knowledge about how the chemical composition and architecture of these NPs influence their thermal sensitivity impedes further optimization. To shed light on this, we have systematically studied their emission intensity, PL decay time curves, absolute PL quantum yield, and thermal sensitivity as a function of the core chemical composition and size, active-shell, and outer-inert-shell thicknesses. The results revealed the crucial contribution of each of these factors in optimizing the NP thermal sensitivity. An optimal active shell thickness of around 2 nm and an outer inert shell of 3.5 nm maximize the PL lifetime and the thermal response of the NPs due to the competition between the temperature-dependent back energy transfer, the surface quenching effects, and the confinement of active ions in a thin layer. These findings pave the way for a rational design of RENPs with optimal thermal sensitivity.

Thermoresponsive Polymeric Nanolenses Magnify the Thermal Sensitivity of Single Upconverting Nanoparticles.

Lanthanide-based upconverting nanoparticles (UCNPs) are trustworthy workhorses in luminescent nanothermometry. The use of UCNPs-based nanothermometers has enabled the determination of the thermal properties of cell membranes and monitoring of in vivo thermal therapies in real time. However, UCNPs boast low thermal sensitivity and brightness, which, along with the difficulty in controlling individual UCNP remotely, make them less than ideal nanothermometers at the single-particle level. In this work, it is shown how these problems can be elegantly solved using a thermoresponsive polymeric coating. Upon decorating the surface of NaYF4 :Er3+ ,Yb3+ UCNPs with poly(N-isopropylacrylamide) (PNIPAM), a >10-fold enhancement in optical forces is observed, allowing stable trapping and manipulation of a single UCNP in the physiological temperature range (20-45 °C). This optical force improvement is accompanied by a significant enhancement of the thermal sensitivity- a maximum value of 8% °C+1 at 32 °C induced by the collapse of PNIPAM. Numerical simulations reveal that the enhancement in thermal sensitivity mainly stems from the high-refractive-index polymeric coating that behaves as a nanolens of high numerical aperture. The results in this work demonstrate how UCNP nanothermometers can be further improved by an adequate surface decoration and open a new avenue toward highly sensitive single-particle nanothermometry.

Boosting the Near-Infrared Emission of Ag2S Nanoparticles by a Controllable Surface Treatment for Bioimaging Applications.

Ag2S nanoparticles are the staple for high-resolution preclinical imaging and sensing owing to their photochemical stability, low toxicity, and photoluminescence (PL) in the second near-infrared biological window. Unfortunately, Ag2S nanoparticles exhibit a low PL efficiency attributed to their defective surface chemistry, which curbs their translation into the clinics. To address this shortcoming, we present a simple methodology that allows to improve the PL quantum yield from 2 to 10%, which is accompanied by a PL lifetime lengthening from 0.7 to 3.8 µs. Elemental mapping and X-ray photoelectron spectroscopy indicate that the PL enhancement is related to the partial removal of sulfur atoms from the nanoparticle's surface, reducing surface traps responsible for nonradiative de-excitation processes. This interpretation is further backed by theoretical modeling. The acquired knowledge about the nanoparticles' surface chemistry is used to optimize the procedure to transfer the nanoparticles into aqueous media, obtaining water-dispersible Ag2S nanoparticles that maintain excellent PL properties. Finally, we compare the performance of these nanoparticles with other near-infrared luminescent probes in a set of in vitro and in vivo experiments, which demonstrates not only their cytocompatibility but also their superb optical properties when they are used in vivo, affording higher resolution images.

Upconverting Nanoparticles in Aqueous Media: Not a Dead-End Road. Avoiding Degradation by Using Hydrophobic Polymer Shells.

The stunning optical properties of upconverting nanoparticles (UCNPs) have inspired promising biomedical technologies. Nevertheless, their transfer to aqueous media is often accompanied by intense luminescence quenching, partial dissolution by water, and even complete degradation by molecules such as phosphates. Currently, these are major issues hampering the translation of UCNPs to the clinic. In this work, a strategy is developed to coat and protect ß-NaYF4 UCNPs against these effects, by growing a hydrophobic polymer shell (HPS) through miniemulsion polymerization of styrene (St), or St and methyl methacrylate mixtures. This allows one to obtain single core@shell UCNPs@HPS with a final diameter of ≈60-70 nm. Stability studies reveal that these HPSs serve as a very effective barrier, impeding polar molecules to affect UCNPs optical properties. Even more, it allows UCNPs to withstand aggressive conditions such as high dilutions (5 µg mL-1 ), high phosphate concentrations (100 mm), and high temperatures (70 °C). The physicochemical characterizations prove the potential of HPSs to overcome the current limitations of UCNPs. This strategy, which can be applied to other nanomaterials with similar limitations, paves the way toward more stable and reliable UCNPs with applications in life sciences.

In Vivo Near-Infrared Imaging Using Ternary Selenide Semiconductor Nanoparticles with an Uncommon Crystal Structure.

The implementation of in vivo fluorescence imaging as a reliable diagnostic imaging modality at the clinical level is still far from reality. Plenty of work remains ahead to provide medical practitioners with solid proof of the potential advantages of this imaging technique. To do so, one of the key objectives is to better the optical performance of dedicated contrast agents, thus improving the resolution and penetration depth achievable. This direction is followed here and the use of a novel AgInSe2 nanoparticle-based contrast agent (nanocapsule) is reported for fluorescence imaging. The use of an Ag2 Se seeds-mediated synthesis method allows stabilizing an uncommon orthorhombic crystal structure, which endows the material with emission in the second biological window (1000-1400 nm), where deeper penetration in tissues is achieved. The nanocapsules, obtained via phospholipid-assisted encapsulation of the AgInSe2 nanoparticles, comply with the mandatory requisites for an imaging contrast agent-colloidal stability and negligible toxicity-and show superior brightness compared with widely used Ag2 S nanoparticles. Imaging experiments point to the great potential of the novel AgInSe2 -based nanocapsules for high-resolution, whole-body in vivo imaging. Their extended permanence time within blood vessels make them especially suitable for prolonged imaging of the cardiovascular system.

Reaching Deeper: Absolute In Vivo Thermal Reading of Liver by Combining Superbright Ag2S Nanothermometers and In Silico Simulations.

Luminescent nano-thermometry is a fast-developing technique with great potential for in vivo sensing, diagnosis, and therapy. Unfortunately, it presents serious limitations. The luminescence generated by nanothermometers, from which thermal readout is obtained, is strongly distorted by the attenuation induced by tissues. Such distortions lead to low signal levels and entangle absolute and reliable thermal monitoring of internal organs. Overcoming both limitations requires the use of high-brightness luminescent nanothermometers and adopting more complex approaches for temperature estimation. In this work, it is demonstrated how superbright Ag2S nanothermometers can provide in vivo, reliable, and absolute thermal reading of the liver during laser-induced hyperthermia. For that, a new procedure is designed in which thermal readout is obtained from the combination of in vivo transient thermometry measurements and in silico simulations. The synergy between in vivo and in silico measurements has made it possible to assess relevant numbers such as the efficiency of hyperthermia processes, the total heat energy deposited in the liver, and the relative contribution of Ag2S nanoparticles to liver heating. This work provides a new way for absolute thermal sensing of internal organs with potential application not only to hyperthermia processes but also to advanced diagnosis and therapy.

Oligonucleotide sensor based on magnetic capture and photoligation of upconverting nanoparticles in solid surfaces.

In this work, we present a luminescence platform that can be used as point of care system for determining the presence and concentration of specific oligonucleotide sequences. This sensor exhibited a limit of detection as low as 50 fM by means of: (i) the use of single-stranded DNA (ssDNA) functionalized magnetic microparticles that captured and concentrated ssDNA-upconverting nanoparticles (ssDNA-UCNPs) on a solid support, when the target sequence (miR-21-5p DNA-analogue) was in the sample, and (ii) a photoligation reaction that covalently linked the ssDNA-UCNPs and the ssDNA magnetic microparticles, allowing stringent washes. The presented sensor showed a similar limit of detection when the assays were conducted in samples containing total miRNA extracted from human serum, demonstrating its suitability for detecting small specific oligonucleotide sequences under real-like conditions. The strategy of combining UCNPs, magnetic microparticles, and a photoligation reaction provides new insight into low-cost, rapid, and ultra-sensitive detection of oligonucleotide sequences.

Ultrafast photochemistry produces superbright short-wave infrared dots for low-dose in vivo imaging.

Optical probes operating in the second near-infrared window (NIR-II, 1,000-1,700 nm), where tissues are highly transparent, have expanded the applicability of fluorescence in the biomedical field. NIR-II fluorescence enables deep-tissue imaging with micrometric resolution in animal models, but is limited by the low brightness of NIR-II probes, which prevents imaging at low excitation intensities and fluorophore concentrations. Here, we present a new generation of probes (Ag2S superdots) derived from chemically synthesized Ag2S dots, on which a protective shell is grown by femtosecond laser irradiation. This shell reduces the structural defects, causing an 80-fold enhancement of the quantum yield. PEGylated Ag2S superdots enable deep-tissue in vivo imaging at low excitation intensities (<10 mW cm-2) and doses (<0.5 mg kg-1), emerging as unrivaled contrast agents for NIR-II preclinical bioimaging. These results establish an approach for developing superbright NIR-II contrast agents based on the synergy between chemical synthesis and ultrafast laser processing.

Contribution of resonance energy transfer to the luminescence quenching of upconversion nanoparticles with graphene oxide.

Upconversion nanoparticles (UCNP) are increasingly used due to their advantages over conventional fluorophores, and their use as resonance energy transfer (RET) donors has permitted their application as biosensors when they are combined with appropriate RET acceptors such as graphene oxide (GO). However, there is a lack of knowledge about the design and influence that GO composition produces over the quenching of these nanoparticles that in turn will define their performance as sensors. In this work, we have analysed the total quenching efficiency, as well as the actual values corresponding to the RET process between UCNPs and GO sheets with three different chemical compositions. Our findings indicate that excitation and emission absorption by GO sheets are the major contributor to the observed luminescence quenching in these systems. This challenges the general assumption that UCNPs luminescence deactivation by GO is caused by RET. Furthermore, RET efficiency has been theoretically calculated by means of a semiclassical model considering the different nonradiative energy transfer rates from each Er3+ ion to the GO thin film. These theoretical results highlight the relevance of the relative positions of the Er3+ ions inside the UCNP with respect to the GO sheet in order to explain the RET-induced efficiency measurements.

10-Fold Quantum Yield Improvement of Ag2S Nanoparticles by Fine Compositional Tuning.

Ag2S semiconductor nanoparticles (NPs) are near-infrared luminescent probes with outstanding properties (good biocompatibility, optimum spectral operation range, and easy biofunctionalization) that make them ideal probes for in vivo imaging. Ag2S NPs have, indeed, made possible amazing challenges including in vivo brain imaging and advanced diagnosis of the cardiovascular system. Despite the continuous redesign of synthesis routes, the emission quantum yield (QY) of Ag2S NPs is typically below 0.2%. This leads to a low luminescent brightness that avoids their translation into the clinics. In this work, an innovative synthetic methodology that permits a 10-fold increment in the absolute QY from 0.2 up to 2.3% is presented. Such an increment in the QY is accompanied by an enlargement of photoluminescence lifetimes from 184 to 1200 ns. The optimized synthetic route presented here is based on a fine control over both the Ag core and the Ag/S ratio within the NPs. Such control reduces the density of structural defects and decreases the nonradiative pathways. In addition, we demonstrate that the superior performance of the Ag2S NPs allows for high-contrast in vivo bioimaging.

Control of upconversion luminescence by gold nanoparticle size: from quenching to enhancement.

Metallic nanostructures have the potential to modify the anti-Stokes emission of upconverting nanoparticles (UCNPs) by coupling their plasmon resonance with either the excitation or the emission wavelength of the UCNPs. In this regard gold nanoparticles (AuNPs) have often been used in sensors for UCNP luminescence quenching or enhancement, although systematic studies are still needed in order to design optimal UCNP-AuNP based biosensors. Amidst mixed experimental evidence of quenching or enhancement, two key factors arise: the nanoparticle distance and nanoparticle size. In this work, we synthesize AuNPs of different sizes to assess their influence on the luminescence of UCNPs. We find that strong luminescence quenching due to resonance energy transfer is preferentially achieved for small AuNPs, peaking at an optimal size. A further increase in the AuNP size is accompanied by a reduction of luminescence quenching due to an incipient plasmonic enhancement effect. This enhancement counterbalances the luminescence quenching effect at the biggest tested AuNP size. The experimental findings are theoretically validated by studying the decay rate of the UCNP emitters near a gold nanoparticle using both a classical phenomenological model and the finite-difference time-domain method. Results from this study establish general guidelines to consider when designing sensors based on UCNPs-AuNPs as donor-quencher pairs, and suggest the potential of plasmon-induced luminescence enhancement as a sensing strategy.

Oligonucleotide Sensor Based on Selective Capture of Upconversion Nanoparticles Triggered by Target-Induced DNA Interstrand Ligand Reaction.

We present a sensor that exploits the phenomenon of upconversion luminescence to detect the presence of specific sequences of small oligonucleotides such as miRNAs among others. The sensor is based on NaYF4:Yb,Er@SiO2 nanoparticles functionalized with ssDNA that contain azide groups on the 3' ends. In the presence of a target sequence, interstrand ligation is possible via the click-reaction between one azide of the upconversion probe and a DBCO-ssDNA-biotin probe present in the solution. As a result of this specific and selective process, biotin is covalently attached to the surface of the upconversion nanoparticles. The presence of biotin on the surface of the nanoparticles allows their selective capture on a streptavidin-coated support, giving a luminescent signal proportional to the amount of target strands present in the test samples. With the aim of studying the analytical properties of the sensor, total RNA samples were extracted from healthy mosquitoes and were spiked-in with a specific target sequence at different concentrations. The result of these experiments revealed that the sensor was able to detect 10-17 moles per well (100 fM) of the target sequence in mixtures containing 100 ng of total RNA per well. A similar limit of detection was found for spiked human serum samples, demonstrating the suitability of the sensor for detecting specific sequences of small oligonucleotides under real conditions. In contrast, in the presence of noncomplementary sequences or sequences having mismatches, the luminescent signal was negligible or conspicuously reduced.

Thermally induced all-optical inverter and dynamic hysteresis loops in graphene oxide dispersions.

We experimentally study the temporal dynamics of amplitude-modulated laser beams propagating through a water dispersion of graphene oxide sheets in a fiber-to-fiber U-bench. Nonlinear refraction induced in the sample by thermal effects leads to both phase reversing of the transmitted signals and dynamic hysteresis in the input-output power curves. A theoretical model including beam propagation and thermal lensing dynamics reproduces the experimental findings.

Electrostatic and hydrodynamics effects in a sedimented magnetorheological suspension.

We present experimental results on the equilibrium microstructure of a sedimented magnetorheological suspension, namely, an aqueous suspension of micron-sized superparamagnetic particles. We develop a study of the electrical interactions on the suspension by processing video-microscopy images of the sedimented particles. We calculate the pair distribution function, g(r), which yields the electrostatic pair potential u(r), showing an anomalous attractive interaction for distances on the order of twice the particle diameter, with characteristic parameters whose values show a dependence with the two-dimensional concentration of particles. The repulsive body of the potential is adjusted to a DLVO expression in order to calculate the Debye screening length and the effective surface charge density. Influence of confinement and variations on the Boltzmann sedimentation profile because of the electrostatic interactions appear to be essential for the interpretation of experimental results.

Morphology of anisotropic chains in a magneto-rheological fluid during aggregation and disaggregation processes.

We study the morphology of the chain-like aggregates formed when a external constant and uniaxial magnetic field is applied to a magneto-rheological (MR) fluid. In order to characterize the conformation of the aggregates, we study the evolution of various fractal dimensions during aggregation and disaggregation processes (i.e., when the applied field is switched on and off), using video-microscopy and image analysis. Experiments have been performed by varying the values of two external parameters: the magnetic field amplitude and particle concentration. We found that the box-counting dimension, related with how the aggregates occupy the surrounding space, depends on the ratio R(1)/R(0). During the first stage of the disaggregation process, when the particles are moving by Brownian motion inside the aggregate, Family-Vicsek scaling function is verified.

Observation of large 10-Gb/s SBS slow light delay with low distortion using an optimized gain profile.

An optimum SBS gain profile is designed to achieve better slow-light performance. It consists of a nearly flat-top profile with sharp edges. Tunable delays up to 3 pulse widths for 100-ps-long input pulses, corresponding to 10 Gb/s data rates, are found while keeping an output-input pulse-width ratio below 1.8. Bit-error-rate (BER) measurements performed for a non-return-to-zero modulation format demonstrates 28 ps of delay under error-free operation.

Modulation-frequency-controlled change from sub- to superluminal regime in highly doped erbium fibers.

We report a change from sub- to superluminal propagation upon increasing the modulation frequency of an amplitude-modulated 1,550 nm signal when propagating through highly doped erbium fibers pumped at 980 nm. We show that the interplay between the pump absorption and the pump-power broadening of the spectral hole induced by coherent population oscillations may drastically affect the fractional advancement or delay of the signal for the considered fibers.

Scaling in the aggregation dynamics of a magnetorheological fluid.

We present experimental results on the aggregation dynamics of a magnetorheological fluid, namely, an aqueous suspension of micrometer-sized superparamagnetic particles, under the action of a constant uniaxial magnetic field using video microscopy and image analysis. We find a scaling behavior in several variables describing the aggregation kinetics. The data agree well with the Family-Vicsek scaling ansatz for diffusion-limited cluster-cluster aggregation. The kinetic exponents z and z' are obtained from the temporal evolution of the mean cluster size S(t) and the number of clusters N(t), respectively. The crossover exponent Delta is calculated in two ways: first, from the initial slope of the scaling function; second, from the evolution of the nonaggregated particles, n1(t). We report on results of Brownian two-dimensional dynamics simulations and compare the results with the experiments. Finally, we discuss the differences obtained between the kinetic exponents in terms of the variation in the crossover exponent and relate this behavior to the physical interpretation of the crossover exponent.

Dynamic transition from modelike patterns to turbulentlike patterns in a broad-area Nd:YAG laser.

We report the first experimental observation to our knowledge of a dynamic transition from modelike patterns to completely disordered patterns in a large-aspect-ratio Nd:YAG laser. Recordings of near-field patterns with an integration time as small as 1 ns allow us to follow the evolution of the transverse intensity profile along the output pulse of the laser.