Rafik Naccache

Temperature sensing using fluorescent nanothermometers.

Acquiring the temperature of a single living cell is not a trivial task. In this paper, we devise a novel nanothermometer, capable of accurately determining the temperature of solutions as well as biological systems such as HeLa cancer cells. The nanothermometer is based on the temperature-sensitive fluorescence of NaYF(4):Er(3+),Yb(3+) nanoparticles, where the intensity ratio of the green fluorescence bands of the Er(3+) dopant ions ((2)H(11/2) --> (4)I(15/2) and (4)S(3/2) --> (4)I(15/2)) changes with temperature. The nanothermometers were first used to obtain thermal profiles created when heating a colloidal solution of NaYF(4):Er(3+),Yb(3+) nanoparticles in water using a pump-probe experiment. Following incubation of the nanoparticles with HeLa cervical cancer cells and their subsequent uptake, the fluorescent nanothermometers measured the internal temperature of the living cell from 25 degrees C to its thermally induced death at 45 degrees C.

Lanthanide-doped NaxScF3+ x nanocrystals : crystal structure evolution and multicolor tuning

Rare-earth-based nanomaterials have recently drawn considerable attention because of their unique energy upconversion (UC) capabilities. However, studies of Sc(3+)-based nanomaterials are still absent. Herein we report the synthesis and fine control of Na(x)ScF(3+x) nanocrystals by tuning of the ratio of oleic acid (OA, polar surfactant) to 1-octadecene (OD, nonpolar solvent). When the OA:OD ratio was increased from low (3:17) to high (3:7), the nanocrystals changed from pure monoclinic phase (Na(3)ScF(6)) to pure hexagonal phase (NaScF(4)) via a transition stage at an intermediate OA:OD ratio (3:9) where a mixture of nanocrystals in monoclinic and hexagonal phases was obtained and the coexistence of the two phases inside individual nanocrystals was also observed. More significantly, because of the small radius of Sc(3+), Na(x)ScF(3+x):Yb/Er nanocrystals show different UC emission from that of NaYF(4):Yb/Er nanocrystals, which broadens the applications of rare-earth-based nanomaterials ranging from optical communications to disease diagnosis.

CdSe Quantum Dots for Two-Photon Fluorescence Thermal Imaging

The technological development of quantum dots has ushered in a new era in fluorescence bioimaging, which was propelled with the advent of novel multiphoton fluorescence microscopes. Here, the potential use of CdSe quantum dots has been evaluated as fluorescent nanothermometers for two-photon fluorescence microscopy. In addition to the enhancement in spatial resolution inherent to any multiphoton excitation processes, two-photon (near-infrared) excitation leads to a temperature sensitivity of the emission intensity much higher than that achieved under one-photon (visible) excitation. The peak emission wavelength is also temperature sensitive, providing an additional approach for thermal imaging, which is particularly interesting for systems where nanoparticles are not homogeneously dispersed. On the basis of these superior thermal sensitivity properties of the two-photon excited fluorescence, we have demonstrated the ability of CdSe quantum dots to image a temperature gradient artificially created in a biocompatible fluid (phosphate-buffered saline) and also their ability to measure an intracellular temperature increase externally induced in a single living cell.

Water dispersible ultra-small multifunctional KGdF4:Tm3+, Yb3+ nanoparticles with near-infrared to near-infrared upconversion

Ultra-small multifunctional KGdF4:Tm3+,Yb3+ nanoparticles with near-infrared to near-infrared upconversion are synthesized. The average sizes of KGdF4:Tm3+ 2%, Yb3+ 20% core-only and KGdF4:Tm3+ 2%, Yb3+ 20%/KGdF4 core–shell nanoparticles are ∼3.7 nm and ∼7.4 nm, respectively, which fall within the reported optimal sizes (<10 nm) for bioimaging probes. The excitation and emission at 980 and 803 nm are favorable to deeper tissue penetration and reduced autofluorescence. The weak upconversion luminescence of the ultra-small core-only nanoparticles is overcome by the use of the core–shell approach. The magnetic mass susceptibility and magnetization of the ultra-small core-only and core–shell nanoparticles were determined, and are close to those of large nanoparticles (26 and 50 nm) used for magnetic resonance imaging and bio-separation. There is no variation in the magnetic properties with the nanoparticles’ sizes between the core-only (∼3.7 nm) and core–shell (∼7.4 nm) nanoparticles, which differs from the size-dependent luminescence. The oleate-capped core–shell nanoparticles were further encapsulated with a PEG-phospholipid shell to endow them with dispersibility in water, which is indispensable for future biological applications.

Nanoparticles for highly efficient multiphoton fluorescence bioimaging

In this paper, we demonstrate for the first time that the new class of fluoride-based inorganic upconverting nanoparticles, NaYF4:Er3+, Yb3+, are the most efficient multiphoton excited fluorescent nanoparticles developed to date. The near-infrared-to-visible conversion efficiency of the aforementioned nanoparticles surpasses that of CdSe quantum dots and gold nanorods, which are the commercially available inorganic fluorescent nanoprobes presently used for multiphoton fluorescence bioimaging. The results presented here open new perspectives for the implementation of fluorescence tomography by multiphoton fluorescence imaging.

Structural and optical investigation of colloidal Ln3+/Yb3+ co-doped KY3F10 nanocrystals

We report for the first time the synthesis of colloidal Ln3+/Yb3+ co-doped KY3F10nanocrystals (Ln = Er or Eu) viathermal decomposition. The transmission electron microscopy (TEM) studies indicated that the average size of the nanocrystals was approximately 15 nm. The nanocrystals crystallized in the cubic Fmm space group as confirmed by Rietveld refinement of the X-ray powder diffraction patterns and by electron diffraction analysis. The Eu3+ ion was used as a spectroscopic probe and its emission spectrum in colloidal KY3F10nanocrystals showed that the lanthanide ions replaces Y3+ in the lattice structure. When co-doped with Er3+/Yb3+, colloidal KY3F10nanocrystals exhibited visible (green and red) upconversion emissions following 978 nm excitation with a near-infrared (NIR) diode laser. Power dependence studies indicated that a two-photon energy transfer upconversion process was responsible for the NIR-to-visible upconversion.

Sensitized Ce3+ and Gd3+ Ultraviolet Emissions by Tm3+ in Colloidal LiYF4 Nanocrystals

The interest in lanthanide (Ln)-doped luminescent nanoparticles has experienced a surge within the scientific community due to their potential integration into a myriad of applications and technologies, with much of the interest stemming from their use as optical probes in biological systems. These nanoparticles offer not only the ability to improve on existing technologies, but also the promise of miniaturization. In principle Ln-doped nanoparticles are suitable for many of these applications because they exhibit sharp emissions arising from intra-4f transitions, which are less influenced by the surrounding crystal fields. Moreover, the Ln ion dopants possess closely spaced energy levels, which assist in converting low-energy near-infrared (NIR) excitation photons into higher-energy visible or UV photons by a process known as upconversion. This conversion of NIR to visible and/or UV light can be easily exploited to tailor the generation of specific emissions that are attractive for a multitude of applications. For example, the additive primary colors (red, green, and blue) can be generated by excitation of Er and Tm-doped systems; it can be envisioned that highly efficient upconverting nanoparticles are poised to impact the display industry. In addition, the prospect of the synthesis of water-dispersible upconverting nanoparticles is of potentially great interest to the life sciences. Colloidal luminescent nanoparticles, dispersed in biorelevant media, allow for the evaluation of various biological systems, particularly in cell imaging, disease detection and treatment, or even substrate monitoring. The UV-generated upconversion emission can also be used in the field of biomedicine, in which UV emissions contribute towards the production of singlet oxygen for photodynamic therapies. Furthermore, the UV emission can also be advantageous in the development of materials for solution-based scintillators. The upconversion process has been widely studied in various nanoscale host matrices, such as oxides, fluorides, and phosphates. Among these nanomatrices, fluorides are particularly attractive not only due to their low-energy phonons, which lead to increased luminescence efficiency, but also due to the availability of several synthetic routes to synthesize them in the colloidal form. In particular, studies on Ln-doped NaYF4 nanocrystals have dominated the literature. For example, bright blue, green, red, and multicolor emissions were observed in Ln-doped NaYF4 nanocrystals. Most of the upconversion studies focus on converting NIR photons to visible ones, but studies reporting on UV emissions from NIR photons are very limited. Another excellent host material for Ln ions and especially for upconversion is LiYF4, which has not been studied in great detail at the nanoscale. Recently, we have observed strong UV emissions by upconversion in Tm/Yb-doped LiYF4 colloidal nanocrystals. [19] However, it would be interesting to extend the study and determine if the upconverted UV emissions can sensitize other ions, such as the Gd ion because its lowest energy excited state lies in the UV region or the Ce ion in which the allowed f!d transition is also in the UV region of the spectrum. Although the sensitization of Gd or Ce ions have been observed following NIR upconversion, to the best of our knowledge it has not been reported in colloidal nanocrystals by upconversion. The use of colloidal nanoparticles could allow for the implementation of NIR-to-UV upconverting nanoparticles in biology due to their small size, which would thus allow them to interact with biological species at similar length scales. Furthermore, their surface chemistry can be tailored for specific applications (i.e., with recognition ligands and antibodies) by altering the surface-capping ligands. Herein, we report the synthesis of Gd/Tm/Ybdoped LiYF4 and Ce /Tm/Yb-doped LiYF4 nanocrys[a] Dr. V. Mahalingam, R. Naccache, Dr. F. Vetrone, Prof. J. A. Capobianco Department of Chemistry and Biochemistry Concordia University 7141 Sherbrooke St. W. Montreal, QC, H4B 1R6 (Canada) Fax: (+1) 514-848-2868 E-mail : capo@vax2.concordia.ca Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200901371.

High Resolution Fluorescence Imaging of Cancers Using Lanthanide Ion-Doped Upconverting Nanocrystals

During the last decade inorganic luminescent nanoparticles that emit visible light under near infrared (NIR) excitation (in the biological window) have played a relevant role for high resolution imaging of cancer. Indeed, semiconductor quantum dots (QDs) and metal nanoparticles, mostly gold nanorods (GNRs), are already commercially available for this purpose. In this work we review the role which is being played by a relatively new class of nanoparticles, based on lanthanide ion doped nanocrystals, to target and image cancer cells using upconversion fluorescence microscopy. These nanoparticles are insulating nanocrystals that are usually doped with small percentages of two different rare earth (lanthanide) ions: The excited donor ions (usually Yb3+ ion) that absorb the NIR excitation and the acceptor ions (usually Er3+, Ho3+ or Tm3+), that are responsible for the emitted visible (or also near infrared) radiation. The higher conversion efficiency of these nanoparticles in respect to those based on QDs and GNRs, as well as the almost independent excitation/emission properties from the particle size, make them particularly promising for fluorescence imaging. The different approaches of these novel nanoparticles devoted to “in vitro” and “in vivo” cancer imaging, selective targeting and treatment are examined in this review.

Optical trapping of NaYF4:Er3+,Yb3+ upconverting fluorescent nanoparticles

We report on the first experimental observation of stable optical trapping of dielectric NaYF4:Er(3+),Yb(3+) upconverting fluorescent nanoparticles (~26 nm in diameter) using a continuous wave 980 nm single-beam laser. The laser serves both to optically trap and to excite visible luminescence from the nanoparticles. Sequential loading of individual nanoparticles into the trap is observed from the analysis of the emitted luminescence. We demonstrate that the trapping strength and the number of individual nanoparticles trapped are dictated by both the laser power and nanoparticle density. The possible contribution of thermal effects has been investigated by performing trapping experiment in both heavy water and into distilled water. For the case of heavy water, thermal gradients are negligible and optical forces dominate the trap loading behaviour. The results provide a promising path towards real three dimensional manipulation of single NaYF4:Er(3+),Yb(3+) nanoparticles for precise fluorescence sensing in biophotonics experiments.

Enhancing the color purity of the green upconversion emission from Er3+/Yb3+-doped GdVO4 nanocrystals via tuning of the sensitizer concentration

Here we report on the enhancement of the intensity of the green/red emission ratio in Er3+/Yb3+-doped GdVO4 nanocrystals obtained via the upconversion process. The nanocrystals were synthesized using a sol–gel process followed by a solid-state reaction. A series of samples bearing different sensitizer ion (Yb3+) concentrations were studied and characterized. Tripositive erbium (Er3+)-doped GdVO4 shows two strong emissions in the green region near 525 and 550 nm while a relatively weak red emission is centred at 660 nm. A 5-fold increase in the intensity of the green/red emission ratio is observed for the Er3+/Yb3+-doped GdVO4 sample co-doped with 20 mol% Yb3+ concentration in comparison to a similar sample without any Yb3+. This suggests a corresponding increase in the color purity of the green emission and as a consequence, this material would be an interesting candidate as a phosphor for display and LED applications.