Fluorescence has become an essential observable in Biology and Medicine. The discrimination of a fluorescent label usually relies on optimizing its brightness and its spectral properties. Despite its widespread use, this approach still suffers from important limitations. First, extraction of a fluorescent signal is challenging in light-scattering and autofluorescent samples. Second, spectral deconvolution of overlapping absorption and emission bands can only discriminate a few labels, which strongly limits the discriminative power of emerging genetic engineering strategies, and falls short from the several tens needed for advanced bioimaging and highly multiplexed diagnostic assays. Our consortium of chemists, physicists, and biologists introduces the HIGHLIGHT concept (PHase-sensItive imaGing of reversibly pHotoswitchable Labels after modulatIon of activatinG ligHT) to achieve chromatic aberration-free highly multiplexed fluorescence imaging with only single and dual wavelength channels in emission and excitation. HIGHLIGHT aims at expanding the discriminative dimensions of fluorophore sets much beyond spectral and concentration information such as classically implemented in multicolor labeling approaches. In HIGHLIGHT, label discrimination will not necessitate anymore singular spectroscopic signatures, sophisticated reading-out instruments, or delicate data processing for signal unmixing. In contrast, it shifts towards designing reactive schemes and observables to selectively promote and retrieve the response of a targeted label. HIGHLIGHT exploits reversibly photoswitchable fluorescent proteins (RSFPs) as labels. Increasingly exploited in super-resolution microscopy and dynamic contrast, they are not only fluorescent but as well engaged in rich photocycles. The HIGHLIGHT protocols exploit their specific fluorescence responses to light modulation under well-designed conditions, which provides several dimensions of dynamic contrast to overcome the limitations encountered with spectral discrimination; These responses will serve as readouts either alone or combined using statistical machine learning strategies, which will enable us to perform real time multiplexed imaging of more than ten spectrally similar fluorescent labels and discriminate more than one hundred hues created by mixing these labels in variable amounts and cell territories. As a proof of principle, we propose to challenge HIGHLIGHT in two types of contexts where the paucity of spectrally distinct fluorescent markers has until now been a major hindrance: the analysis of the lineage of retinal cell subtypes and that of their connectivity. In this project, we will namely (i) design and implement a suite of transgenic tools enabling to express varied combinations of 6-12 RSFPs within a population of cells; (ii) design HIGHLIGHT protocols for wide-field and scanning microscopies as well as relevant barcoding strategies to discriminate different cells; (iii) evaluate the photoswitching properties of several tens of RSFPs with one- and two-photon excitation under various environments; (iv) validate HIGHLIGHT for its implementation in a commercial confocal microscope and in state-of-the art Single Plane Illumination scanning Microscopes to push forward acquisition depth and speed; and eventually (v) perform multiplexed clonal analysis in the vertebrate retina, and single-neuron tracing and analysis of axonal convergence. Eventually, the tools and protocols introduced in this project will have near-universal applicability in Biology for multiplexed fluorescence-based observations within biological samples.

EDMs, i.e. electric dipole moments of electrons, neutrons or nuclei are sensitive probes for new physics beyond the Standard Model of particle physics. In the present project, we propose to measure the EDM of those systems embedded in a cryogenic solid matrix of inert gas or hydrogen. Matrices offer unprecedented sample sizes while maintaining characteristics of an atomic physics experiment, such as the possibility of manipulation by lasers. An EDM experiment on molecules in inert gas matrices has the potential to reach a statistical sensitivity of the order of 1e–36 e cm; a value beyond that of any other proposed technique. With this project, in a strong collaboration between experimental (LAC, ISMO,LPL) and theoretical (CIMAP) groups, we first aim at performing a detailed investigation of all limiting effects (mainly the ones limiting the optical pumping performance and coherence time) using Cs atoms. This should provide a first proof of principle EDM measurement and set the ground for precise study of systematic effects which will allow EDMMA to reach unprecedented precision

Phase Change Random Access Memories (PCRAM), which are based on the reversible amorphous-crystalline transition in phase change materials (PCMs), constitute a very promising alternative to Flash technology, which is reaching fundamental limits. One of their key advantages is their scalability but, for ultimate miniaturization, energy consumption is critical and a promising solution is the geometrical confinement of the memory points. Mastering this with PCMs at ultimate dimensions (typically 5 nm) is, however, a real challenge, which calls for a fundamental understanding of the interplay between strain (the amorphous-to-crystal transition is accompanied by density increase of several %) and interface energies at the nanoscale. The objective of the SESAME project is to study the influence of strain and size on the PCM phase transition at ultimate dimensions. To address these issues we will use advanced in situ characterization techniques applied to ultra-thin layers, confined nanostructures and nanoclusters in order to investigate the early stages of phase transition and also to measure local strains and microstructure changes at crystallization. Five partners with complementary know-how will participate in the project: IM2NP-Marseille, CEA-LETI-Grenoble, CEA-INAC-Grenoble, synchrotron SOLEIL – St Aubin, CINaM-Marseille. The SESAME project will be organized along 5 tasks: 1. Coordination, 2. Sample preparation and characterization, 3. High resolution synchrotron X-ray scattering, 4. Transmission Electron Microscopy (TEM), 5. Simulation. Thin/ultra-thin GeTe and Ge2Sb2Te5 (GST) PCM films and PCM materials in confined structures will be prepared at CEA-LETI. Various thickness (100 to 5 nm), size (down to 10 nm width) and capping materials (Ta, TaN, Ta2O5, SiN, SiO2, Ti, TiN …) will be studied. CEA-INAC has the unique capability of preparing sub-10 nm GeTe and GST clusters by gas phase condensation. This will allow us to address the ultimate sizes, far beyond existing capabilities of lithography. Clusters with different composition or doping will be embedded in matrices with various thermo mechanical properties in order to evaluate the impact of mechanical stress on PCM clusters properties. Preliminary in situ sample characterizations will be performed at CEA: in situ ellipsometry, reflectivity, Raman spectroscopy or four-point-probe resistivity measurements. On these well-characterized samples unique in situ High-resolution synchrotron x-ray scattering and state-of-the-art transmission Electron microscopy (TEM) investigations will be performed. An original combination of resistance, X-ray diffraction and X-ray reflectivity that allows correlating structural and electrical PCM properties upon crystallization has been developed jointly by IM2NP and ESRF and will be used at synchrotron SOLEIL to characterize in situ the phase transition of ultrathin PCMs. Also the in situ combination of X-ray diffraction and optical curvature measurements developed jointly by IM2NP and DiffAbs beamline at SOLEIL will allow for an in-depth understanding of the mechanics involved in the amorphous-to-crystal transition. State-of-the-art TEM performed at CEA-INAC and CEA-LETI will bring valuable knowledge on local distribution of elements, defects and strains. In situ TEM observations during crystallization will offer invaluable information on the nucleation sites for crystallization. It is worth noting that these highly original in situ techniques (based either on TEM or Synchrotron radiation) will be used also to investigate structural changes in the amorphous phase. The issue of resistance drift in the amorphous phase is a key point for the stability of stored information in the memory cell. Atomistic simulations (Density Functional Theory, Molecular Dynamics) will be performed at CINaM in order to simulate the atomistic structure and the properties (structural, electronic, spectroscopic) of phase change materials in amorphous and crystalline form.

Ice phases incorporating a non-negligible amount of salt have been recently experimentally demonstrated. In particular, both high- and low-pressure phases have been reported, showing interest respectively in models for planetary interior compositions, and solid aqueous electrolytes for battery devices. Investigating these phases in greater detail and potentially identifying new ones is therefore interesting both for fundamental and applied research perspectives. Since high-pressure characterization experiments are challenging, atomic-scale numerical simulations such as molecular dynamics can help providing valuable insights in the formation and stability of materials. Four challenges prevent reaching a quantitative description of salty ice phases through atom scale modeling: the computational cost of ab initio approaches, the subtle balance of interactions in water, the low accuracy and transferability of empirical potentials, and the selection of an appropriate collective variable to follow transformations between phases. The SIMODAS project aims at solving all four challenges, by combining two data-driven approaches: one to derive optimal collective variables, and one to extract accurate and transferable interaction potentials. With this methodology in hand, the formation processes and stability field of a range of salty ices will be investigated. In particular, several halides will be considered, to extract knowledge regarding the necessary conditions for the favorable formation of crystallines phases. In addition, work will be devoted to characterize the ion transport properties of these phases to provide valuable information for planetary models and materials design for electrolytes. Finally, several methodological improvements related to the committor probability will be investigated, ranging from accelerating its estimation from molecular dynamics simulations, to investigating local approximations enabling significant dimensionality reduction in optimizing collective variables.

More than two decades ago has emerged a new technology exploiting electron spins to convey information within an electric circuitry. This technology, known as spintronics, translates in advantages such as nonvolatile storage technology, fast-data processing speed and low-power consumption. The working principle of a spintronic device is to generate a non-equilibrium spin population and to detect it. However, creation and detection occurs in different regions of the device. During the transfer process from one region to the other, the spin population tends to relax towards its non spin-polarized equilibrium state weakening then the efficiency of the device. One of the central research areas in spintronics therefore aims at perfecting this transfer process. Present efforts involve improving existing technology or finding novel radical ways of manipulating spin-polarized electrons. The SPINCOMM project is in line with this second approach and falls in the context of molecular spintronics. The purpose of project SPINCOMM is to carry out the first fundamental investigation of spin transport across a single organometallic wire. To achieve this ambitious goal, a pioneering bottom-up approach will be implemented through four innovating strategies: 1) SIMPLIFICATION: The wires will have a multi-decker architecture where single transition-metal atoms alternate with cyclopentadienyl rings (C5H5). Strikingly, these wires have been predicted to display a 100% spin-filtering efficiency over a wide bias range. 2) CONTROL: Transport measurements will be carried out with a low-temperature scanning tunneling microscope (STM) operated in ultrahigh vacuum. The molecules will be deposited onto a well-calibrated surface and then contacted by the STM tip. Junction formation with a single multi-decker molecule will be greatly facilitated by the upstanding adsorption geometry onto the surface. Precise information about the binding properties of the multi-decker molecule to the electrodes will be available. XMCD measurements will be carried out independently to carefully characterize the magnetic status of the molecules. 3) CUSTOMIZATION: The chemical composition of the molecule and its length will be modified directly in the STM junction to optimize spin transport. Moreover, the material of tip and surface will be changed in order to tackle different aspects of spin transport. These essentially consist in the Kondo effect (non-magnetic tip and surface) and its interplay with spin-polarized electrons (ferromagnetic tip and a non-magnetic surface), as well as a transport across a single-molecule spin-valve (ferromagnetic tip and surface). 4) SIMULATION: Given the unprecedented microscopic control exerted over the junction and the simplified molecular architecture employed, the experimental data will be highly amenable to first-principle calculations. State-of-the-art density functional theory and transport calculations will be used to unravel the key mechanisms governing spin transport, along with non-equilibrium and correlated calculations to treat the Kondo problem. With the know-how acquired, the mono-decker architecture of the molecule will be exploited for developing a new spin-sensitive microscopy. A molecular tip comprising a mono-decker molecule will be used to record “contact images” of the surface. Surfaces with opposite magnetizations are expected to produce a higher contrast than the one accessible to SP-STM due to the nearly ideal spin-filtering effect of the mono-decker molecule. With spin-polarized contact microscopy it will be possible to map the spin-polarized properties of surfaces and nanostructures with atomic-scale spatial resolution and to assess the impact of defects, surface impurities, and electronic inhomogeneities on spin transport. We expect this technique to develop quickly and to have a success similar to one of SP-STM in these last ten years.