Our objective is to design in this three-year project an original “lab-on-fiber” tool for remote, label-free “in vivo” molecular analysis that could be dedicated in the future to endoscopic diagnosis. While micro-arrays are currently used “in vitro” for multi-parametric detections of biomarkers, concerning “in vivo” molecular detection, no multi-parametric label-free approach has been developed so far. Nonetheless this tool could be very useful and bring significant progress in the medical field especially in diagnosis technique like endoscopy. This tool could efficiently complete this imaging medical analysis. Indeed, the diagnosis would be facilitated by the real time detection, quantification, and localization of specific pathologies’ biomarkers. This tool-associated gain could highly benefit to the patients and significantly reduce the overall cost of diagnosis. To achieve this project our approach is based on functionalized nanotextured optical fiber bundles. When appropriately designed and covered by a gold layer those nanostructured fibers exhibit interesting plasmonic properties. We wish to take advantage of those optical properties to perform remote biological analysis. For this, we plan to design an array of different biological probes at the nanotextured bundle end face to confer specific bio-sensing properties. The so formed device will be used “in vivo” for biological targets multiplexed specific detection in a remote mode. This project is highly interdisciplinary as it combines skills at the forefront of optics, electrochemistry, surface chemistry, biochemistry, nano- and micro-technologies applied to the biological field. The work will be done by four complementary research groups (ISM / NSYSA, SPRAM / CREAB, LAAS / NBS, IAB/ AICD). The main steps of the project are schematically presented below. The fibers bundles will be etched and metalized in ISM (Bordeaux). This group is specialized in the development of new analytical nanosystems for biological applications by combining mainly optical and electrochemical techniques at the nanometer scale. LAAS (Toulouse) will provide patterning tools for the localized biofunctionalization of fibers surfaces by means of e.g. micromachined cantilevers thanks to their skills in micro- and nanotechnologies. SPRAM (Grenoble) will develop a dedicated optical setup in order to characterize the sensitivity of the designed probe. SPRAM has an expertise in the field of surface plasmon resonance (SPR) bio-chip functionalization and instrumentation development. IAB (Grenoble) studies the immune system and its digressions in chronic pathologies associated to inflammations. They will provide the required knowledge to qualify the bundles in model tissue before validating the tool efficiency for “in vivo” multiplexed molecular detection in an endoscopic and minimally-invasive way in a mouse model.

Graphene isolation in 2004 and the following apparition of the related 2D materials family (h-BN, transition metal dichalcogenides (TMDC)) open up the way to novel high performance electronic devices. One-atomic-layer-thick 2D materials can be artificially stacked nearly at will, creating heterostructures that combine the properties of each constituent. The J2D project aims at creating heterojunctions using different types of 2D materials (metal, semiconductor, insulator) to explore the interface properties at the atomic scale and correlate them to photo-transport measurements. It covers all the steps from materials to device, focusing on fundamental issues. At each stage, different experimental techniques (AFM, STM, KPFM, Raman, Photoluminescence, transport) and modeling will be coupled in a back and forth way to benefit from each other and help choose the best direction for the next step. Materials will be either grown in situ - by CVD on different types of substrate or by SiC graphitisation - or exfoliated and then characterized by different experimental techniques and ab initio modeling to determine their crystalline quality, size and check for their electronic properties. In situ growth will be developed for TMDC monolayer ( in-plane junctions while transfer will enable vertical structures. The consortium already masters exfoliation of many of the 2D materials and graphene growth on different substrate. The approaches will be adapted to tackle TMDC and possible in plane re-epitaxy. Van der Waals stacking either by micromanipulation or in situ by CVD will then be used to create heterostructures (step 2). We already have the skills for transfer of graphene and will have to extend them to other 2D materials. The electronic, optic and transport properties of the van der Waals stacked heterostructures will be studied in step 3. For each of the 3 first steps, related practical but core questions will be addressed: doping of materials (since this has been the key in semiconductor electronics for many years), stacking orientation and possible species trapping between transferred layers during the stacking step , effect of true 2D character in junctions since all junctions model are for 3D. Beyond classical 3D designs (pn junctions, Schottky junctions, field effect transistor) that have been the building blocks of the electronic industry since its beginning, new geometries and new concepts enabled by 2D will be explored such as truly 2D quantum wells for original devices (light emitting diode) in the fourth step. Each task of the project will provide materials for popularization with a main goal, explain to a broad audience what two-dimensionality means and offers. This will take the form of a demonstrator for the physiquarium, a popularization platform developed at Institut Néel with an augmented reality nanomanipulator simulator to make visitors “feel” differences between Van der Waals and covalent bonds and lead to a reflexion on bonding. The scientific expertise of the three partners (Institut Néel, LPTM, SPrAM) in 2D materials, their complementary skills covering all the steps and their already existing relationships ensure the success of the project.

Our health depends in many cases of the course of our immune response. It organizes the body's defenses against infections, is involved in the mechanisms of inflammatory and autoimmune diseases, the elimination of cancer cells, transplant rejection ... The precise definition of the functions of immune cells, particularly of their secretions, is of interest for both better diagnosis and adjustment of medicines within immunotherapies. Among these cells, lymphocytes play a key role, particularly through the production of cytokines (destruction of infected cells, antibody production ...). These monodisperse and non-adherent cells are besides suitable for handling in a microfluidic system. Biosensors can enable their study at the scale of the individual cell but multi-scale analytical systems for the study, within the same device, of biological objects of different sizes such as one cell (about 10 microns) and its secreted proteins (nanometric) are still research concerns. The challenge to make these analytic microdevices efficient is in the development of their architecture which must include multistage detection for cells and secretions. For twenty years, the use of functionalized pores has emerged as a method for biosensing reaching higher sensitivities than conventional methods. It is therefore suitable for the serial detection of very small amounts of samples. In this project, we propose to develop multiscale biosensors based on a network of pores i) of different sizes (10-100 microns and 10-200 nm) and ii) functionalized with recognition biomolecules for the specific capture of lymphocytes and the detection of their secretions. We have developed in 2009 a novel technique called CLEF (ContactLess ElectroFunctionalization) which allows fast, one-step and very localized grafting of biomolecules on the walls of a perforated pore (micro and nanopores) in a semiconductor material coated with a dielectric layer. However, these "through" pores, because of their 3D configuration, i) have a great complexity of manufacture and implementation, ii) do not allow further analyses using pores positioned in series for cascade detections, iii) are not compatible with standard optical detection techniques, iv) do not allow parallelization of the analysis and a multiplexing of the measurement. To overcome these limitations, we propose to use a two-dimensional pore technology based on the restriction of a microfluidic channel, named 2D pore, and to demonstrate the feasibility of CLEF for their localized functionalization. 2D pores will be designed using lithographic techniques on a microfluidic chip and CLEF will be implemented using microelectrodes placed in the fluidic channels close to the pores. The design of multiscale biosensors will then be envisioned with different sized pores successions for the combined detection of lymphocytes and their secretions. The microelectrodes located in the fluidic channels will allow the electrical detection of secretions of lymphocytes in nanopores. Biochemical interactions in each pore can also be detected by fluorescence microscopy due to the easy optical observation permitted by the glass covering of the chip. The 2D format of this multi-scale sensor allows to consider parallelized analysis to simultaneously process a large number of samples. This generic biosensor for dynamic multi-scale detection can adapt to any type of cell / secretions and bacteria / toxins biological model, and thus cover a wide range of healthcare applications.

Metalorganic lead halide perovskites have emerged recently as a very promising class of materials for photovoltaics. Perovskite solar cells combine high efficiency (>20%) with ultra-low cost fabrication via low temperature solution processes and have a high potential for use e.g. in building integrated photovoltaics. Yet, the main drawbacks to be overcome for making out of the scientific breakthrough a real technology are (a) the presence of lead, (b) the limited understanding of detrimental processes (e.g. device hysteresis) and (c) the limited stability. SuperSansPlomb addresses the following key issues: i) Coherent design of lead-free perovskites using combined theoretical and experimental screening; ii) Device integration and study of the fundamental processes governing the charge generation and transfer in the lead-free perovskite solar cells; iii) Development of selective contacts and blocking layers yielding optimized solar cell performance and long term stability.