The RESONATE project aims at developing laser-grade rare-earth cubic sesquioxides (hereafter called RESO or cRE2O3 : of composition Y2O3, Gd2O3, Lu2O3) single crystals doped with rare-earth (RE) ions, like Yb3+. Recent studies on cRE2O3 single crystals and ceramics have demonstrated the laser potential of these materials and highlighted the extreme thermodynamic conditions under which their growth takes place (very high powders and gases purities, very high temperatures, H2-containing gas mixtures to slow down the expensive Re crucible dissolution). The RESONATE project proposes to develop a cheap, simple, reliable and safe crystal growth process of these materials by the widely spread flux method, using an original and non toxic solvent and growth setup design operative in air and at half the melting temperature of RESO. Obviously, such a growth process has an edge over other traditional and classical methods and we believe that RESONATE will make it mature very rapidly. Yb3+-doped cRE2O3 single crystals will allow for the determination of the basic spectroscopic and laser parameters necessary to understand and optimize the laser performances of the various cRE2O3-based solid-state laser cavities (high-power and ultrafast lasers based on Yb3+-doped materials). To achieve this goal, the RESONATE project will particularly rely on single crystal spectroscopic and laser studies, for which the Institut d’Optique of Palaiseau has accepted to join the project. The RESONATE project, structured in three interdependent scientific tasks, requires the recruitment of a post-doctoral fellow, for the last two years of the project, for the growth and characterizations of Yb3+-doped cRE2O3 single-crystals. By associating this post-doctoral fellow with four young researchers and engineers well-versed in crystal growth techniques, crystallographic characterizations and physical properties measurements, and with two engineer-assistants of outstanding craftmanship, the RESONATE project possesses the relevant knowledge, know-how and manpower that will allow for its success. The fact that ALPhA-Route des Lasers has given its seal of approval to the RESONATE project may be looked upon as an indication of its reliability. In addition, as the RESONATE participants are permanent staff of the ICMCB, the RESONATE research team and the approaches developed within are very likely to be perpetuated. The post-doctoral research fellow will benefit from scientific and technical environments absolutely unique in France. As a matter of fact, the 250 m2 crystal growth national facility “CGNF” project has been awarded in february 2009 the quality label of the two complementary and closely interlinked organizations the ICMCB belongs to, namely the Scientific Groupment Interest (GIS “Advanced Materials in Aquitaine”) and the Materials and Systems Institute of Bordeaux (MIB Carnot Institute).

The ultimate sensitivity in imaging biological phenomenon in live cells is achieved by single-molecule detection, generally based on luminescence. Single-molecule methods have changed the way we think and carry out experiments on complex molecular systems by providing access to distributions of molecular properties which is of importance in biological systems that display static or time-dependent heterogeneity. Single-molecule detection also provides the possibility to determine molecule positions with nanometer accuracies, far below the optical resolution. The current luminescence-based single molecule techniques however suffer major limitations: short live times of probes (fluorescent molecules), large probe size (nanoparticles) but also the difficulty to detect the 3D trajectories of single molecules as well as the inability to detect single molecules in thick living samples where the interference from cellular autofluorescence is severe. In this context, the need for small nano-labels with red-shifted optical responses appeared crucial for further applications single molecule methods to tissues. A class of nanomaterials displays strong optical resonances in the nearIR: single wall carbon nanotubes (SWNTs). SWNTs are characterized by a high ratio of length (hundreds of nanometers up to millimeters) over diameter (~1nm). The discovery of their strong fluorescence in the nearIR opened the possibility to directly detect them at the single molecule level. They also bear remarkable absorption properties and could be detected at the single molecule level by a photothermal method that we recently developed. Their cell penetrating properties raised recently great hopes for applications in drug delivery. To serve as nanoprobes, standard SWNTs are nevertheless not readily applicable due to their long 1D dimension (>100nm) despite their unique optical properties. Interestingly, ultrashort (<10nm) SWNTs (UshortNTs) have been recently processed and their ensemble luminescence in the nearIR has been observed. We strongly believe that UshortNTs constitute promising nearIR nanolabels for 3D single molecule detection in tissues providing that specific microscopy methods and nanotube chemistry are now developed. In this project, we propose to develop new 3D single molecule tracking schemes of UshortNTs (which will be based on luminescence and photothermal detection), to bio-functionalize them and to apply them to study the spatio-temporal organization of neurotransmitters receptors in brain slices. Indeed, an important application of single molecule microscopy concerns the study of neurotransmitter receptors trafficking between sub-cellular compartments which play a key role in neuronal physiology, e.g. during synaptic plasticity. Over the last years, we have demonstrated the invaluable power of single molecule detection for understanding the complexity and key role of receptor diffusion processes in and out of the synapses of neurons. However, since “standard” single molecule methods still suffer from the previously mentioned limitations, current approaches are inappropriate for recording accurately the full 3D movements of a single receptor, especially in brain slices. This is a strong limitation because fluxes of receptors in and out synapses not only involve lateral diffusion in the plane of the membrane, but also endo/exocytosis and intracellular trafficking. As well, little is known about receptor dynamics in intact neuronal networks constituted e.g. by brain slices. The main biological outcome of this project will thus to perform such studies. More generally, this will constitute the first single molecule study in thick living tissues and this new approach should be transposable to many important biological questions. The cytotoxicity of the UshortNTs will also be studied in this project.