Thermometric Analysis of Nanoaperture-Trapped Erbium-Containing Nanocrystals.

Temperature changes in plasmonic traps can affect biomolecules and quantum emitters; therefore, several works have sought out the capability of measuring the local temperature. Those works used ionic nanopore currents, fluorescence emission variations, and fluorescence-based diffusion tracking to measure the temperature dependence of shaped nanoapertures in metal films. Here, we make use of a stable erbium-containing NaYF4 nanocrystal that gives local temperature dependence while trapped in the nanoaperture hot spot. Ratiometric analysis of the emission at different wavelengths gives local temperature variation. Since the gold film dominates the thermal characteristic, we find that films of thickness 70, 100, and 130 nm give 0.64, 0.37, and 0.25 K/mW temperature change with laser power. Therefore, using thicker films can be effective in reducing the heating when it is not desired.

X-ray-Sensitive Doped CaF2-Based MRI Contrast Agents for Local Radiation Dose Measurement.

Ionizing radiation has become widely used in medicine, with application in diagnostic techniques, such as computed tomography (CT) and radiation therapy (RT), where X-rays are used to diagnose and treat tumors. The X-rays used in CT and, in particular, in RT can have harmful side effects; hence, an accurate determination of the delivered radiation dose is of utmost importance to minimize any damage to healthy tissues. For this, medical specialists mostly rely on theoretical predictions of the delivered dose or external measurements of the dose. To extend the practical use of ionizing radiation-based medical techniques, such as magnetic resonance imaging (MRI)-guided RT, a more precise measurement of the internal radiation dose internally is required. In this work, a novel approach is presented to measure dose in liquids for potential future in vivo applications. The strategy relies on MRI contrast agents (CAs) that provide a dose-sensitive signal. The demonstrated materials are (citrate-capped) CaF2 nanoparticles (NPs) doped with Eu3+ or Fe2+/Fe3+ ions. Free electrons generated by ionizing radiation allow the reduction of Eu3+, which produces a very small contrast in MRI, to Eu2+, which induces a strong contrast. Oxidative species generated by high-energy X-rays can be measured indirectly using Fe2+ because it oxidizes to Fe3+, increasing the contrast in MRI. Notably, in the results, a strong increase in the proton relaxation rates is observed for the Eu3+-doped NPs at 40 kV. At 6 MV, a significant increase in proton relaxation rates is observed using CaF2 NPs doped with Fe2+/Fe3+ after irradiation. The presented concept shows great promise for use in the clinic to measure in vivo local ionizing radiation dose, as these CAs can be intravenously injected in a saline solution.

Contrast Enhancement in MRI Using Combined Double Action Contrast Agents and Image Post-Processing in the Breast Cancer Model.

Gd- and Fe-based contrast agents reduce T1 and T2 relaxation times, respectively, are frequently used in MRI, providing improved cancer detection. Recently, contrast agents changing both T1/T2 times, based on core/shell nanoparticles, have been introduced. Although advantages of the T1/T2 agents were shown, MR image contrast of cancerous versus normal adjacent tissue induced by these agents has not yet been analyzed in detail as authors considered changes in cancer MR signal or signal-to-noise ratio after contrast injection rather than changes in signal differences between cancer and normal adjacent tissue. Furthermore, the potential advantages of T1/T2 contrast agents using image manipulation such as subtraction or addition have not been yet discussed in detail. Therefore, we performed theoretical calculations of MR signal in a tumor model using T1-weighted, T2-weighted, and combined images for T1-, T2-, and T1/T2-targeted contrast agents. The results from the tumor model are followed by in vivo experiments using core/shell NaDyF4/NaGdF4 nanoparticles as T1/T2 non-targeted contrast agent in the animal model of triple negative breast cancer. The results show that subtraction of T2-weighted from T1-weighted MR images provides additional increase in the tumor contrast: over two-fold in the tumor model and 12% in the in vivo experiment.

Isolating and enhancing single-photon emitters for 1550 nm quantum light sources using double nanohole optical tweezers.

Single-photon sources are required for quantum technologies and can be created from individual atoms and atom-like defects. Erbium ions produce single photons at low-loss fiber optic wavelengths, but they have low emission rates, making them challenging to isolate reliably. Here, we tune the size of gold double nanoholes (DNHs) to enhance the emission of single erbium emitters, achieving 50× enhancement over rectangular apertures previously demonstrated. This produces enough enhancement to show emission from single nanocrystals at wavelengths not seen in our previous work, i.e., 400 and 1550 nm. We observe discrete levels of emission for nanocrystals with low numbers of emitters and demonstrate isolating single emitters. We describe how the trapping time is proportional to the enhancement factor for a given DNH structure, giving us an independent way to measure the enhancement. This shows a promising path to achieving single emitter sources at 1550 nm.

Target-Specific Magnetic Resonance Imaging of Human Prostate Adenocarcinoma Using NaDyF4-NaGdF4 Core-Shell Nanoparticles.

We illustrate the development of NaDyF4-NaGdF4 core-shell nanoparticles (NPs) for targeting prostate cancer cells using a preclinical 9.4 T magnetic resonance imaging (MRI) of live animals. The NPs composed of paramagnetic Dy3+ and Gd3+ (T2- and T1-contrast agents, respectively) demonstrate proton relaxivities of r1 = 20.2 mM-1 s-1 and r2 = 32.3 mM-1 s-1 at clinical 3 T and r1 = 9.4 mM-1 s-1 and r2 = 144.7 mM-1 s-1 at preclinical 9.4 T. The corresponding relaxivity values per NP are r1 = 19.4 × 105 mMNP-1 s-1 and r2 = 33.0 × 105 mMNP-1 s-1 at 3 T and r1 = 9.0 × 105 mMNP-1 s-1 and r2 = 147.0 × 105 mMNP-1 s-1 at 9.4 T. In vivo active targeting of human prostate tumors grown in nude mice revealed docking of anti-prostate-specific membrane antigen (PSMA) antibody-tagged NPs at tumor sites post-24 h of their intravenous injection. On the other hand, in vivo passive targeting showed preferential accumulation of NPs at tumor sites only within 2 h of their injection, ascribed to the enhanced permeation and retention effect of the tumor. A biodistribution study employing the harvested organs of mice, post-24 h injection of NPs, quantified active targeting as nearly twice as efficient as passive targeting. These outcomes provide potential opportunities for noninvasive diagnosis using NaDyF4-NaGdF4 core-shell NPs for target-specific MRI.

Photon-counting computed tomography of lanthanide contrast agents with a high-flux 330-µm-pitch cadmium zinc telluride detector in a table-top system.

Purpose: We present photon-counting computed tomography (PCCT) imaging of contrast agent triplets similar in atomic number ( Z ) achieved with a high-flux cadmium zinc telluride (CZT) detector. Approach: The table-top PCCT imaging system included a 330 - µ m -pitch CZT detector of size 8 mm × 24 mm 2 capable of using six energy bins. Four 3D-printed 3-cm-diameter phantoms each contained seven 6-mm-diameter vials with water and low and high concentration solutions of various contrast agents. Lanthanum ( Z = 57 ), gadolinium (Gd) ( Z = 64 ), and lutetium ( Z = 71 ) were imaged together and so were iodine ( Z = 53 ), Gd, and holmium ( Z = 67 ). Each phantom was imaged with 1-mm aluminum-filtered 120-kVp cone beam x rays to produce six energy-binned computed tomography (CT) images. Results: K -edge images were reconstructed using a weighted sum of six CT images, which distinguished each contrast agent with a root-mean-square error (RMSE) of < 0.29 % and 0.51% for the 0.5% and 5% concentrations, respectively. Minimal cross-contamination in each K -edge image was seen, with RMSE values < 0.27 % in vials with no contrast. Conclusion: This is the first preliminary demonstration of simultaneously imaging three similar Z contrast agents with a difference in Z as low as 3.

Isolating Nanocrystals with an Individual Erbium Emitter: A Route to a Stable Single-Photon Source at 1550 nm Wavelength.

Single-photon emitters based on individual atoms or individual atomic-like defects are highly sought-after components for future quantum technologies. A key challenge in this field is how to isolate just one such emitter; the best approaches still have an active emitter yield of only 50% so that deterministic integration of single active emitters is not yet possible. Here, we demonstrate the ability to isolate individual erbium emitters embedded in 20 nm nanocrystals of NaYF4 using plasmonic aperture optical tweezers. The optical tweezers capture the nanocrystal, whereas the plasmonic aperture enhances the emission of the Er and allows the measurement of discrete emission rate values corresponding to different numbers of erbium ions. Three separate synthesis runs show near-Poissonian distribution in the discrete levels of emission yield that correspond to the expected ion concentrations, indicating that the yield of active emitters is approximately 80%. Fortunately, the trap allows for selecting the nanocrystals with only a single emitter, and so this gives a route to isolating and integrating single emitters in a deterministic way. This demonstration is a promising step toward single-photon quantum information technologies that utilize single ions in a solid-state medium, particularly because Er emits in the low-loss fiber-optic 1550 nm telecom band.

Resonant Plasmon-Enhanced Upconversion in Monolayers of Core-Shell Nanocrystals: Role of Shell Thickness.

The upconversion luminescence (UCL) of colloidal lanthanide-doped upconversion nanocrystals (UCNCs) can be improved either by precise encapsulation of the surface by optically inert shells around the core, by an alteration of the nearby environment via metal nanoparticles, or by a combination of both. Considering their potential importance in crystalline silicon photovoltaics, the present study investigates both effects for two-dimensional arrangements of UCNCs. Using excitation light of 1500 nm wavelength, we study the variation in the upconversion luminescence from an Er3+-doped NaYF4 core as a function of the thickness of a NaLuF4 shell in colloidal solutions as well as in spin-cast-assisted self-assembled monolayers of UCNCs. The observed UCL yields and decay times of Er3+ ions of the UCNCs increase with increasing shell thickness in both cases, and nearly no variation in decay times is observed in the transition of the UCNCs from solution to film configurations. The luminescence efficiency of the UCNC monolayers is further enhanced by electron-beam-lithographic-designed Au nanodiscs deposited either on top of or buried within the monolayer. It is observed that the improvement by the nanocrystal shells is greater than that of the Au nanodiscs.

Halide-, Hybrid-, and Perovskite-Functionalized Light Absorbing Quantum Materials of p-i-n Heterojunction Solar Cells.

The p-i-n quantum dot (QD) solar cells were fabricated through the single-step deposition of both of its p-type and light absorbing quantum layers. The hole transport and light absorbing layers of these devices were made by the p- and n-type PbS QDs, which were functionalized with mercaptopropionic acid and different halide, hybrid, and perovskite ligands, respectively. Fabrication of such p-i-n devices by the single-step deposition of pre-exchanged colloidal QDs had not been fully investigated so far because of the low progression of ligand exchange processes, weak colloidal stability of pre-exchanged QDs in desired solvents, and remaining of the ligand exchange products along with particles. However, we showed that the type of ligand complexes, amino acid products of ligand exchange, and protic solvents are highly effective for increasing the ligand exchange progression and preparation of high colloidal stability QDs with superior photoluminescence properties. As well, the surface chemistry investigations by the means of Fourier transform infrared, nuclear magnetic resonance, X-ray photoelectron spectroscopy, X-ray diffraction, inductively coupled plasma optical emission spectrometry, carbon-hydrogen-nitrogen-sulfur elemental analysis, zeta potential, and high-resolution transmission electron microscopy were led to the presentation of new concepts about the theoretical and experimental ligand weight percentages, the mechanisms of solution-phase ligand exchange processes, and formation of ligands adlayer on the (111) facets of QDs. The pre-exchanged colloidal QDs showed very good desirability for the single-step deposition of dense, defects-free, and smooth QD layers. Regarding that, the p-i-n solar cells were successfully fabricated by the single-step deposition of both of the QD layers. Especially, the highest power conversion efficiency value of 6.40% was recorded for the devices in which the light absorbing layer was prepared by the composite-like QD-perovskite structures.

Site-specific conjugation of the quencher on peptide's N-terminal for the synthesis of a targeted non-spreading activatable optical probe.

Optical imaging offers high sensitivity and portability at low cost. The design of 'smart' or 'activatable' probes can decrease the background noise and increase the specificity of the signal. By conjugating a fluorescent dye and a compatible quencher on each side of an enzyme's substrate, the signal remains in its 'off ' state until it reaches the area where a specific enzyme is expressed. However, the signal can leak from that area unless the dye is attached to a molecule able to bind to a specific target also presented in that area. The aim of this study was to (i) specifically conjugate the quencher on the α-amino group of the peptide's N-terminus, (ii) conjugate the dye on the ε-amino group of a lysine in C-terminus, and (iii) conjugate the carboxyl group of the peptide's C-terminus to an amino group present on an antibody, using carbodiimide chemistry. The use of protecting groups, such as Boc or Fmoc, to allow site-specific conjugation, presents several drawbacks including 'on beads labeling', additional steps required for deprotection and removal from the resin, decreased yield, and dye degradation. A method of preferential labeling of α-amino N-terminal group in slightly acidic solution, proposed by Selo et al. (1996) has partially solved the problem. The present study reports improvements of the method allowing to (i) avoid the homo-bilabeling, (ii) increase the yield of the N-terminal labeling by two folds, and (iii) decrease the cost by 44-fold. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Polarization-dependent extraordinary optical transmission from upconversion nanoparticles.

Enhanced upconversion (UC) emission was experimentally demonstrated using gold double antenna nanoparticles coupled to nanoslits in gold films. The transmitted red emission from UC ytterbium and erbium co-doped sodium yttrium fluoride (NaYF4:Yb(3+)/Er(3+)) nanoparticles (UC NPs) at ∼665 nm (excited with a 980 nm diode laser) was enhanced relative to the green emission at ∼550 nm. The relatively enhanced UC NP emission could be tuned by the different polarization-dependent extraordinary optical transmission modes coupled to the gold nanostructures. Finite-difference time-domain calculations suggest that the preferential enhanced UC emission is related to a combination of different surface plasmon mode excitation coupling to cavity Fabry-Perot interactions. A maximum UC enhancement of 6-fold was measured for nanoslit arrays in the absence of the double antennas. In the presence of the double nanoantennas inside the nanoslits, the UC enhancement was between 2- and 4-fold, depending on the experimental conditions.

Lanthanide-based heteroepitaxial core-shell nanostructures: compressive versus tensile strain asymmetry.

Heteroepitaxial core-shell nanostructures have been proven advantageous in a wide variety of applications, ranging from luminescence enhancement, band gap engineering, multimodal theranostics, to catalysis. However, precisely tailoring the epitaxial growth is challenging, and a general understanding of the parameters that impact epitaxial growth remains unclear. Here we demonstrate the critical role of the sign of the lattice mismatch of the shell relative to the core (compressed/tensile) in generating lanthanide-based core-shell structures, a parameter conventionally not considered in heteroepitaxial design. We took advantage of the very gradual contraction of lanthanide ions along the series to control precisely both the magnitude and the sign of lattice mismatch and investigated multiple sodium lanthanide fluoride (NaLnF4) core-shell heterostructures of variable composition and size. We discovered that the tensile strained shells adapt to the core crystallite shape (i.e., conformal) and lattice structure (i.e., coherent), while under identical magnitude of mismatch, the compressively strained shells are neither conformal nor coherent to the core. This striking asymmetry between the tensile and compressively strained epitaxial growth arises from the fundamental anharmonicity of the interatomic interactions between the attractive and repulsive pairs. From a broader perspective, our findings redefine the a priori design consideration and provide a fundamental insight on the necessity to include the sign of lattice mismatch and not just its magnitude in designing heteroepitaxial core-shell nanostructures.

Neodymium-doped LaF(3) nanoparticles for fluorescence bioimaging in the second biological window.

The future perspective of fluorescence imaging for real in vivo application are based on novel efficient nanoparticles which is able to emit in the second biological window (1000-1400 nm). In this work, the potential application of Nd(3+) -doped LaF(3) (Nd(3+) :LaF(3) ) nanoparticles is reported for fluorescence bioimaging in both the first and second biological windows based on their three main emission channels of Nd(3+) ions: (4) F(3/2) →(4) I(9/2) , (4) F(3/2) →(4) I(11/2) and (4) F(3/2) →(4) I(13/2) that lead to emissions at around 910, 1050, and 1330 nm, respectively. By systematically comparing the relative emission intensities, penetration depths and subtissue optical dispersion of each transition we propose that optimum subtissue images based on Nd(3+) :LaF(3) nanoparticles are obtained by using the (4) F3/2 →(4) I11/2 (1050 nm) emission band (lying in the second biological window) instead of the traditionally used (4) F(3/2) →(4) I(9/2) (910 nm, in the first biological window). After determining the optimum emission channel, it is used to obtain both in vitro and in vivo images by the controlled incorporation of Nd(3+) :LaF(3) nanoparticles in cancer cells and mice. Nd(3+) :LaF(3)nanoparticles thus emerge as very promising fluorescent nanoprobes for bioimaging in the second biological window.

Size-dependent maximization of upconversion efficiency of citrate-stabilized ß-phase NaYF4:Yb(3+),Er(3+) crystals via annealing.

Upconversion materials show great potential in converting infrared light to visible for many optoelectronic and photovoltaic devices. One of the most promising upconverting materials is Yb(3+),Er(3+)- doped ß-NaYF4. In this study, annealing is shown to have a significant impact on the phase, morphology, and upconversion luminescence of ß-NaYF4:Yb(3+),Er(3+) crystals of varying sizes (300 nm, 700 nm, and 2.3 µm, respectively) prepared by hydrothermal synthesis stabilized with sodium citrate. Upconversion luminescence is maximized via annealing while maintaining crystal shape and size dispersity up to a temperature dependent on initial size, with NIR-to-visible quantum yields of 2-5%. Further temperature increases result in growth and agglomeration, increasing luminescence, followed by transformation to the α-cubic phase resulting in decreases in overall upconversion performance and shifts to dominant red emission. This study establishes the critical link between annealing temperature and maximal upconversion luminescence in ß-NaYF4:Yb(3+),Er(3+) crystals, while maintaining particle morphology, which can be very important for technological application.

Optimal dye-quencher pairs for the design of an "activatable" nanoprobe for optical imaging.

Optical imaging offers high sensitivity and portability at low cost. The design of an optimal "activatable" imaging agent could greatly decrease the background noise and increase specificity of the signal. Five different molecules have been used to quench basal fluorescence of an enzyme substrate labeled with Cy5, Cy5.5 or IR800 at a distance of 8 amino acids (32 Å): a 6 nm gold nanoparticle (NP), a 20 nm and a 30 nm iron oxide (FeO) NP, the black hole quencher BHQ-3 and the IRdye quencher QC-1. The quenching efficiencies were 99% for QC1-IR800, 98% for QC1-Cy5.5, 96% for 30 nm FeO NP-Cy5.5, 89% for BHQ3-Cy5, 84% for BHQ3-Cy5.5, 77-90% for 6 nm gold NP-Cy5.5, depending on the number of dyes around the NP, 79% for 20 nm FeO NP-Cy5.5 and 77% for Cy5.5-Cy5. Signal activation upon cleavage by the matrix metalloproteinase MMP9 was proportional to the quenching efficiencies, ranging from 3-fold with Cy5.5-Cy5 to 67-fold with QC1-IR800. This independent work reports on the properties of the dyes and quenchers explaining the superior performance of QC-1 and 30 nm FeO NPs.

Subtissue thermal sensing based on neodymium-doped LaF3 nanoparticles.

In this work, we report the multifunctional character of neodymium-doped LaF3 core/shell nanoparticles. Because of the spectral overlap of the neodymium emission bands with the transparency windows of human tissues, these nanoparticles emerge as relevant subtissue optical probes. For neodymium contents optimizing the luminescence brightness of Nd³âº:LaF3 nanoparticles, subtissue penetration depths of several millimeters have been demonstrated. At the same time, it has been found that the infrared emission bands of Nd³âº:LaF3 nanoparticles show a remarkable thermal sensitivity, so that they can be advantageously used as luminescent nanothermometers for subtissue thermal sensing. This possibility has been demonstrated in this work: Nd³âº:LaF3 nanoparticles have been used to provide optical control over subtissue temperature in a single-beam plasmonic-mediated heating experiment. In this experiment, gold nanorods are used as nanoheaters while thermal reading is performed by the Nd³âº:LaF3 nanoparticles. The possibility of a real single-beam-controlled subtissue hyperthermia process is, therefore, pointed out.

Synthesis of nanoparticles, their biocompatibility, and toxicity behavior for biomedical applications.

Nanomaterials research has in part been focused on their use in biomedical applications for more than several decades. However, in recent years this field has been developing to a much more advanced stage by carefully controlling the size, shape, and surface-modification of nanoparticles. This review provides an overview of two classes of nanoparticles, namely iron oxide and NaLnF4, and synthesis methods, characterization techniques, study of biocompatibility, toxicity behavior, and applications of iron oxide nanoparticles and NaLnF4 nanoparticles as contrast agents in magnetic resonance imaging. Their optical properties will only briefly be mentioned. Iron oxide nanoparticles show a saturation of magnetization at low field, therefore, the focus will be MLnF4 (Ln = Dy3+, Ho3+, and Gd3+) paramagnetic nanoparticles as alternative contrast agents which can sustain their magnetization at high field. The reason is that more potent contrast agents are needed at magnetic fields higher than 7 T, where most animal MRI is being done these days. Furthermore we observe that the extent of cytotoxicity is not fully understood at present, in part because it is dependent on the size, capping materials, dose of nanoparticles, and surface chemistry, and thus needs optimization of the multidimensional phenomenon. Therefore, it needs further careful investigation before being used in clinical applications.

Ln(3+)-doped nanoparticles for upconversion and magnetic resonance imaging: some critical notes on recent progress and some aspects to be considered.

In this feature article we will critically discuss the synthesis and characterisation aspects of Ln(3+)-doped nanoparticles (NPs) that show upconversion, upon 980 nm excitation. Upconversion is a non-linear process that converts two or more low-energy photons, often near-infrared photons, into one of higher energy, e.g. blue and 800 nm from Tm(3+) and green and red from Er(3+) or Ho(3+). Nearly all researchers use the absorption of 980 nm light by Yb(3+) as the sensitiser for the co-doped emissive Ln(3+) ions. The focus will be on LnF(3) and MLnF(4) (M = alkali metal) as the host matrix, because most progress has been made with these. In particular we will argue that a detailed understanding of how the dopant ions and the host Ln(3+) ions are distributed (in the core) and how (doped) shell growth occurs is not well understood. Moreover, their use as optical and magnetic resonance imaging contrast agents will be discussed. We will argue that deep-tissue imaging beyond 600 µm with retention of optical resolution, i.e. to see fine structure such as blood capillaries in brain tissues, has not yet been achieved. Three key parameters have been identified as impediments: (i) the low absorption efficiency of the Yb(3+) sensitiser, (ii) the low quantum yield of upconversion, and (iii) the long-lived excited states. On the other hand, there are very encouraging results that suggest that these nanoparticles could be developed into very potent magnetic resonance imaging (MRI) contrast agents.

Synthesis of InN@SiO2 nanostructures and fabrication of blue LED devices.

We synthesized InN@SiO(2) nanostructures (i.e., nanoparticles and nanowires) by varying the annealing temperature and nitridation conditions of In(2)O(3)@SiO(2) nanoparticles in the presence of ammonia. The In(2)O(3)@SiO(2) nanoparticles were synthesized using a urea-based homogeneous precipitation of indium hydroxide on the surface of the SiO(2) (15 nm) nanoparticles, followed by annealing at 600 °C in air. Subsequently, nitridation of In(2)O(3)@SiO(2) nanoparticles in ammonia at 600 °C for 2 h resulted in InN@SiO(2) nanoparticles. The sizes of InN nanoparticles are ∼5 nm on the silica surface. Nitridation at the same temperature for 3-5 h gave InN nanoparticles of size ∼20 nm. Furthermore, on annealing above 650 °C the InN nanoparticles grew in the form of nanowires. The nanowires are 4-5 µm in length and have a diameter of 100 nm. The photoluminescence peak of both InN@SiO(2) nanoparticles and nanowires is centered at 442 nm (λ(exi) = 325 nm). Subsequently, the surface of InN@SiO(2) nanoparticles was modified by reacting with dodecyltriethoxysilane at 80 °C, which enabled them to be dispersible in toluene. The surface-modified InN@SiO(2) nanoparticles were used to fabricate blue electroluminescence devices which showed blue electroluminescence peak centered at 442 nm. The Commission Internationale de I'Eclairage (CIE) coordinates of InN@SiO(2) nanoparticles are X = 0.15 and Y = 0.13, which is well within the blue region and commercially appropriate.