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Life at high temperature observed in vitro upon laser heating of gold nanoparticles

Life at high temperature observed in vitro upon laser heating of gold nanoparticles

Thermophiles are microorganisms that thrive at high temperature. Studying them can provide valuable information on how life has adapted to extreme conditions. However, high temperature conditions are difficult to achieve on conventional optical microscopes. Some home-made solutions have been proposed, all based on local resistive electric heating, but no simple commercial solution exists. In this article, we introduce the concept of microscale laser heating over the field of view of a microscope to achieve high temperature for the study of thermophiles, while maintaining the user environment in soft conditions. Microscale heating with moderate laser intensities is achieved using a substrate covered with gold nanoparticles, as biocompatible, efficient light absorbers. The influences of possible microscale fluid convection, cell confinement and centrifugal thermophoretic motion are discussed. The method is demonstrated with two species: (i) Geobacillus stearothermophilus, a motile thermophilic bacterium thriving around 65 °C, which we observed to germinate, grow and swim upon microscale heating and (ii) Sulfolobus shibatae, a hyperthermophilic archaeon living at the optimal temperature of 80 °C. This work opens the path toward simple and safe observation of thermophilic microorganisms using current and accessible microscopy tool

Germination de bactéries thermophiles (Geobacillus stearothermophilus) à partir de spores micrométriques observée par microscopie de front d’onde, et activée par chauffage laser de nanoparticules d’or à 58°C
Copyright Springer Nature 2022.

Reference : Molinaro, C., Bénéfice, M., Gorlas, A. et al. Life at high temperature observed in vitro upon laser heating of gold nanoparticles. Nat Commun 13, 5342 (2022)

Financings : ERC HiPhore

Contact : Guillaume Baffou

Revealing the organisation of actin in cells through the orientation of single molecules

A new polarized imaging approach based on the localization of isolated fluorescent molecules reveals the nanoscale organization of actin in cells. This work is published in the journal Nature Communications.

Single-molecule localization microscopy provides insights into the nanometer-scale spatial organization of proteins in cells, however it does not provide information on their conformation and orientation, which are key functional signatures. Detecting single molecules’ orientation in addition to their localization in cells is still a challenging task, in particular in dense cell samples. Here, we present a polarization-splitting scheme which combines Stochastic Optical Reconstruction Microscopy (STORM) with single molecule 2D orientation and wobbling measurements, without requiring a strong deformation of the imaged point spread function. This method called 4polar-STORM allows, thanks to a control of its detection numerical aperture, to determine both single molecules’ localization and orientation in 2D and to infer their 3D orientation. 4polar-STORM is compatible with relatively high densities of diffraction-limited spots in an image, and is thus ideally placed for the investigation of dense protein assemblies in cells. We demonstrate the potential of this method in dense actin filament organizations driving cell adhesion and motility.

Figure : Nanoscale imaging of actin network organization in cells by 4polar-STORM. Left: orientation image of fluorescent markers (phalloidin, AlexaFluor 488), following the orientation of the actin filaments they report. The colour code corresponds to the orientation of the isolated molecules measured by STORM in super-resolved fluorescence imaging. An assembly of actin filaments is shown schematically. The images on the right represent zooms of cell regions (top: a lamellipod, bottom: stress fibres). The lines represent the average direction in the plane of the sample, explored by a single actin labelling molecule. Scale bars: 300 nm.

Reference : V C. Rimoli, C. Valades Cruz, V. Curcio, M. Mavrakis, S. Brasselet. 4polar-STORM polarized super-resolution imaging of actin filament organization in cells. Nat. Communications 13, 301 (2022)

Financings : France BioImaging National Infrastructure (ANR-10-INBS-04), CENTURI convergence institute (ANR-16-CONV-0001), ANR SEPTIMORF (ANR-17-CE13-0014), ANR 3DPolariSR (ANR-20-CE42-0003). A*MIDEX (ANR-11-IDEX-0001), European Union’s Horizon 2020 research and innovation programme under the Marie SklodowsNewly identified motif explains preferential septin-microtubule associationka-Curie (grant agreement No 713750), INRIA (projet NAVISCOPE-IPL).

Contacts : Sophie Brasselet and Manos MavrakisMOSAIC group, Institut Fresnel, Marseille

Newly identified motif explains preferential septin-microtubule association

The identification of a new motif helps elucidate interactions between septins and microtubules, two essential components of the animal cytoskeleton.

Septins are a family of highly conserved small GTP-binding proteins that associate with cell membranes, actin filaments and microtubules, and are increasingly being recognised as central regulators of cell architecture. Of the thirteen septins found in mammalian cells, septin 9 (SEPT9) uniquely enables interactions with microtubules, but it has been difficult to define the molecular basis that drives this preferential binding. Collaborative work between biologists at the Centre de Recherche en Cancérologie de Marseille and Institut Fresnel and biophysicists at TU Delft (Kuzmić et al. 2022) address this problem by combining functional intracellular studies with in vitro reconstitution assays. The authors show that the binding of septins to microtubules requires a microtubule-associate protein (MAP)-like motif specific to the SEPT9 isoform SEPT9_i1, and that only septin octamers harbouring this isoform bind specifically to dynamic microtubules and slows down their rate of depolymerisation. The authors also design a number of specific genetic variants that modulate the interaction between microtubules and SEPT9_i1, including mutations similar to those that are frequently found in patients affected by the poorly understood hereditary neuralgic amyotrophy. Interestingly, the relocalisation of septin octamers from stress fibres to microtubules causes a proportion of these fibres to be lost from adherent cells and alters their internal tension. These findings shed new light on the molecular determinants of septin association with actin and microtubules and on their consequences on the organisation of the cytoskeleton.

Figure. Fluorescence imaging of septin distribution in animal cells. Left, SEPT9_i1 associates both with actin fibres and microtubules. Middle, a hybrid septin bearing the newly identified motif associates exclusively with microtubules. Right, two point mutations in this motif lead to the loss of microtubule association.

Reference : Kuzmić, M., Castro-Linares, G., Fialová, J., Iv, F., Salaün, D., Llewellyn, A., Gomes, A., Belhabib, M., Liu, Y., Asano, K., Rodrigues, M., Isnardon, D., Tachibana, T., Koenderink, G., Badache, A., Mavrakis, M., and Pascal Verdier-Pinard (2022) Septin-microtubule association via a motif unique to the isoform 1 of septin 9 tunes stress fibers. Journal of Cell Science

Contact : Manos Mavrakis - MOSAIC Group

Partners : This research is the result of collaborative work between Institut Fresnel, Centre de Recherche en Cancérologie de Marseille (CRCM), TU Delft and Osaka University.

Fundings : This research received funding from the Agence Nationale de la Recherche (ANR grant ANR- 17-CE13-0014; SEPTIMORF) and the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO/OCW) through the ‘BaSyC-Building a Synthetic Cell’ Gravitation grant (024.003.019).

Keywords: Actin, Cytoskeleton, Microtubule, Septin, SEPT9

Unlocking the nanoworld of plant cell walls thanks to optical near-field hyperspectral imaging

Plant material is a natural, ecological and renewable resource that is widely exploited, whether in its raw state as a construction material, in its composite state for the paper industry, or in its processed state in biofuels and bioplastics. This biomaterial is very attractive for its mechanical, chemical, thermal and optical properties. However, a major concern in the wood industry is to manage the biodegradability, instability and profitability of this biomaterial by developing chemical and/or physical treatments. These treatments induce local changes in the chemical composition of plant cell walls (PCW), thus affecting their physical and morphological properties.

Despite recent studies on these materials at scales close to molecular distributions, many questions remain unanswered: "How do chemical variations impact physical properties (mechanical, hygroscopic, thermal, optical) at the nanoscale?", "How can the modified physical properties of PCW have a positive impact on the wood industry?

Researchers from the CNRS at the Fresnel Institute and the CINaM in Marseille in collaboration with researchers from the ORNL-Oak Ridge National Lab - USA are providing some answers by using near-field optical microscopy with the partnership with Neaspec Gmbh - Germany. Indeed, if PCWs are composed of elaborate polymeric nano-blocks with complex chemistry, their overall response to light is ultimately coded by the optical scattering from these individual nano-blocks. The detection of near-field optical scattering, via a metallic nanoscale tip, allows access to the structural, chemical and physical properties of these nano-blocks and thus of the cell wall.

Using this microscopy technique coupled with infrared spectroscopy (Neaspec Gmbh), the researchers mapped the cell wall in the mid-infrared with a spatial resolution of less than 20 nm. This work has made it possible to evaluate in situ, for the first time, the local optical properties of the PCW associated with its local chemical and structural variability. This was previously unmeasurable with conventional optical techniques. Only chemical extraction techniques separating the different components of the wall made it possible to obtain a posteriori information on the optical properties of each component of the wall individually, forgetting the impact of its structure and chemical environment.

As a sustainable resource, wood is becoming a material of choice not only for the construction, paper and biofuel markets, but also for the development of intelligent building components, or for the engineering of new plant-based materials. This near-field optical microscopy technique will uniquely facilitate the understanding of wood morphogenesis at the cell walls scale. It will, for example, provide essential information for controlled wood engineering towards the development of biodegradable high-tech components. The high precision control of mechanical and optical properties in wood production remains a major concern towards a more efficient and reasoned use of these biomaterials which have not finished meeting our needs.

Partners: This work is a collaborative work between Institut Fresnel, CINaM, Oak Ridge National Lab & Neaspec society.

Fundings: Idex Aix Marseille - Innovation & Emergence program AAP2017 (N° : A-M-AAP-EI-17-10-170224-18.04-CHARRIER-E), CNRS - PICS 2019 (A. L. LEREU) and BioEnergy Science Center - ORNL.

Reference: “In-situ plant material hyperspectral imaging: determination of chemistry and optical properties using multimodal scattering nearfield optical microscopy”, A. Charrier, A. Normand, A. Passian, P. Schaefer and A. L. Lereu, Comm. Mat., 2, 59 (2021).

 The story is now on Oak Ridge National Laboratory website with the article "International team visualizes properties of plant cell walls at nanoscale"

 Read this article "Behind the paper" in Nature NPG :

Contact: Aude Lereu - RCMO Group

Aider au Diagnostic de la Maladie d’Alzheimer par l’Intelligence Artificielle en Imagerie TEP du Métabolisme du Glucose
Publication et Vidéo dans le New Journal of Physics

La Maladie d’Alzheimer (MA) est l’une des maladies neurodégénératives les plus répandues dans le monde. Elle touche plus de 50 millions de personnes et ce nombre dépassera les 152 millions d’ici 2050, si cette situation perdure, constituant ainsi la principale cause de mortalité chez les personnes âgées. Au stade prodromique un sujet atteint de Trouble Cognitif Léger (TCL) peut évoluer vers la démence. Une des difficultés majeures actuelles est d’identifier, parmi les sujets TCL, ceux qui dans le temps vont développer une démence de type MA.

La Tomographie par Emission de Positrons (TEP) au 18 Fluoro-Deoxy-Glucose est une modalité d’imagerie moléculaire qui contribue au diagnostic précoce de cette maladie, en mesurant la consommation de Glucose des régions anatomiques du cerveau.

L’aide au diagnostic assistée par ordinateur que nous avons développée permet de répondre au défi de l’identification, sur l’image TEP d’un sujet, d’une MA au stade de TCL. A cet effet, un Réseau de Neurones Convolutif (RNC) pyramidal séparable profond est conçu sur la base d’un apprentissage des vues coronales, sagittales et axiales d’images TEP. Cette architecture 2D séparable a permis de réduire considérablement le nombre de paramètres d’apprentissage, comparée au classique RNC 3D, tout en donnant de meilleures performances en termes de taux de bonne classification.

L’approche développée, appliquée à la base de données Alzheimer’s Disease Neuroimaging Initiative (ADNI) montre des très bons résultats (83 % de taux de bonne classification), comparés aux méthodes basées sur l’apprentissage automatique (en moyenne à 76 % de taux de bonne classification)à bases de réseaux de neurones profonds y compris les 3D RNC.

Partenaires : Ces travaux sont le fruit d’une collaboration entre les équipes GSM et IMOTHEP
Organismes financeur : DHU-Imaging
Référence : Xiaoxi Pan; Trong-Le Phan; Mouloud Adel; Caroline Fossati; Thierry Gaidon; Julien Wojak; Eric Guedj, IEEE Transactions on Medical Imaging ( Volume: 40, Issue: 1, Jan. 2021)
Contacts: Mouloud ADEL, Equipe GSM et Eric GUEDJ Equipe IMOTHEP

Spectral expansions of open and dispersive optical systems : Gaussian regularization and convergence

Publication & Video in New Journal of Physics

Given the importance of modal methods in wave physics for describing the properties and dynamics of closed systems in terms of eigenmodes and eigenvalues, physicists have quite naturally sought to describe open systems in terms of open system eigenstates (often called Resonant States or Quasi-Normal-Modes) characterized by complex eigenvalues. Our work invokes the interaction of electromagnetic waves with particles to resolve two technical obstacles confronting such an endeavor.

The first problem we address is how one can define resonant state scalar products despite the fact that Resonant State wave-functions diverge exponentially in the far field. The resolution of this problematic is crucial for defining concepts like orthogonality and normalization for resonant states and has consequently received considerable attention, but we present the merits of a Gaussian regularization technique that can produce fully analytical results in certain circumstances (like scattering from a sphere), and partially analytic results in more general situations. With the scalar product issue resolved, we address another problematic that has been appreciated only quite recently, namely that directly truncated resonant state spectral expansions may `converge’ slowly, or not at all. We propose a solution to this problem that consists of constraining truncated spectral expansions to obey the same analytic structure and conservation laws as the complete solutions.

 Watch this Video on New Journal of Physics website:

Spectral expansions of open and dispersive optical systems : Gaussian regularization and convergence, Brian Stout, Rémi Colom, Nicolas Bonod and Ross Mc Phedran. Published by IOP Publishing Ltd on behalf of the Institute of Physics and Deutsche Physikalische Gesellschaft, New Journal of Physics, Volume 23, August 2021.

Partners: This research is collaborative work between Institut Fresnel and Ross McPhedran, Macquarie University, Australian National University (ANU).

Fundings: This research received funding from LIA ALPHha, Associated Laboratory for Photonics between France and Australia

Contact : Brian STOUT, Team CLARTE

New tools for revealing the organization and function of human septins

Septins constitute a family of proteins involved in a wide range of biological processes, from cell division to cell motility and animal tissue morphogenesis. In human pathophysiology, a role of septins has been established in neuropathies, infertility and tumorigenesis. Despite their essential roles, how human septins organize and function in cells remains poorly understood. Human septins isolated from cells exist in the form of stable heterooctamers containing SEPTIN9. A large body of literature has implicated SEPTIN9 in diverse human cancers. Hereditary neuralgic amyotrophy (HNA), a rare neuropathy, has been mapped to mutations in SEPTIN9. Understanding SEPTIN9 function thus necessitates the study of septins in the context of their physiological assembly into heterooctameric complexes.

To this end, collaborative work between biologists at Institut Fresnel and biophysicists at Institut Curie and TU Delft succeeded to isolate for the first time recombinant heterooctameric human septin complexes containing SEPTIN9. A combination of biochemical and biophysical assays, fluorescence and electron microscopy confirmed the octameric nature of the isolated octamers, and showed that recombinant octamers polymerize into filaments. Reconstitution studies showed that octamers directly bind and cross-link actin filaments, raising the possibility that septin-decorated actin cytoskeleton in cells reflects direct actin-septin interactions. Reconstitution studies of recombinant octamers containing SEPTIN9 with physiological septin interactors, such as membranes and microtubules, promise to provide a powerful complementary approach to cell and animal model studies of septin organization and function.

Iv, F., Silva Martins, C., Castro-Linares, G., Taveneau, C., Barbier, P., Verdier-Pinard, P., Camoin, L., Audebert, S., Tsai, F.-C., Ramond, L., Llewellyn, A., Belhabib, M., Nakazawa, K., Di Cicco, A., Vincentelli, R., Wenger, J., Cabantous, S., Koenderink, G.H., Bertin, A., and Manos Mavrakis (2021) Insights into animal septins using recombinant human septin octamers with distinct SEPT9 isoforms. Journal of Cell Science

Partners: This research is collaborative work between Institut Fresnel, Institut Curie, TU Delft, Centre de Recherche en Cancérologie de Toulouse (CRCT), Centre de Recherche en Cancérologie de Marseille (CRCM), Institut de Neurophysiopathologie (INP), Architecture et Fonction des Macromolécules Biologiques (AFMB), and Monash University.

Fundings: This research received funding from the Agence Nationale de la Recherche (ANR grant ANR-17-CE13-0014; SEPTIMORF), the Fondation ARC pour la recherche sur le cancer (grant PJA 20151203182), the Fondation pour la Recherche Médicale (FRM grant ING20150531962) and the Cancéropôle PACA and INCa. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 723241). This work was further financially supported by the Netherlands Organization for Scientific Research (NWO/OCW) through a VIDI grant (project number: 680-47-233) and the ‘BaSyC—Building a Synthetic Cell’ Gravitation grant (024.003.019), and from two PHC Van Gogh grants (no. 25005UA and no. 28879SJ, Ministères des Affaires Étrangères et de l’Enseignement Supérieur et de la Recherche).

Contact : Manos Mavrakis, MOSAIC Group

Active thermal cloaking and mimicking

Can you feel the heat? An international group of Applied Mathematicians and Physicists has devised a way of making objects invisible to thermal measurements. The novelty in their approach is that they use heat pumps rather than especially crafted materials to hide the objects. A refrigerator is a household example of a heat pump: to cool groceries it pumps heat from the inside to the outside. Using heat pumps is much more flexible than using carefully crafted materials, just as software is much more flexible than hardware. For example the researchers can make one object or source appear as a completely different object or source. So at least from the perspective of thermal measurements they can make an apple appear as an orange.

The work remains theoretical and has the drawback that the probing temperature field must be known ahead of time. However the approach is within reach of current technology by using small heat pumps called Peltier elements that transport heat by passing an electrical current across a metal-metal junction. As for real world applications, the researchers envision their work can be used to accurately control the temperature of an object in space and time. The same Mathematics could enable accurate drug delivery.

Active thermal cloaking and mimicking, Maxence Cassier, Trent DeGiovanni, Sébastien Guenneau and Fernando Guevara Vasquez, Proceedings of the Royal Society of London. Series A.

Keywords: Heat equation, Active Cloaking, Potential Theory, Green identities

Contact: Maxence CASSIER, EPSILON group

Grant: National Science Foundation DMS-2008610

Other Media:
 Article on Imperial College website:

 Article on Utah University website:

Reconfigurable Flat Optics with Programmable Reflection Amplitude Using Lithography-Free Phase-Change Material Ultra-Thin Films

Turning a mirror into an optical absorber

A very large dynamic optical reflection modulation from a simple unpatterned layered stack of phase-change material ultra-thin films is experimentally demonstrated. Specifically, this work demonstrates that properly designed systems comprising deeply subwavelength GeSbTe (GST) films, a dielectric spacer, and a metallic mirror produce a dynamic modulation of light in the near-infrared from very strong reflection (up to 𝑅≈80%
) to perfect absorption ( 𝐴>99.995%) by simply controlling the crystalline state of the phase-change material. While the amplitude of modulation experimentally reaches an optical contrast higher than 104, intermediate levels of reflection in between extreme values can also be actively encoded, corresponding to partial crystallization of the GST layer. Several layered system designs are further explored and guidelines are provided to tailor the efficient wavelength range, the angle of operation, and the degree of crystallization leading to perfect absorption.


Références :
Reconfigurable Flat Optics with Programmable Reflection Amplitude Using Lithography-Free Phase-Change Materials Ultra-Thin Films., S. Cueff, A. Taute, A. Bourgade, J. Lumeau, S. Monfray, Q. Song, P. Genevet, B. Devif, X. Letartre and L. Berguiga, in Advanced Optical Materials 2001291 (2020)

 Retrouvez également l’article consacré à ces travaux sur le site du CNRS - INSIS

Complete electromagnetic dyadic Green function characterization in a complex environment – resonant dipole-dipole interaction and cooperative effects

La fonction de Green joue un rôle central dans la propagation des ondes, car elle décrit la réponse d’un système à une impulsion arbitraire. Cependant, la mesurer expérimentalement est très difficile car il s’agit d’une quantité complexe qui doit être mesurée avec une résolution spatiale nettement sous-longueur d’onde. Ces exigences ont considérablement limité les tentatives expérimentales de mesure de la fonction de Green jusqu’à présent.

Dans le cadre de l’IRP ALPhFA, des chercheurs de notre laboratoire et de l’Institute for Photonics and Optical Sciences (IPOS) de l’Université de Sydney ont mis au point une méthode expérimentale pour mesurer et caractériser pleinement la fonction de Green en enregistrant l’impédance mutuelle entre deux dipôles à des fréquences micro-ondes. L’efficacité de cette approche est démontrée en effectuant ces mesures à l’intérieur d’une cavité planaire résonnante de miroirs parallèles ou non parallèles, à une résolution cent fois inférieure à la longueur d’onde.
Les résultats obtenus sont conformes aux prédictions théoriques, ce qui confirme la validité de cette approche.

Pour en savoir plus sur ces travaux de recherche, consultez l’article disponible ici :

 Complete electromagnetic dyadic Green function characterization in a complex environment – resonant dipole-dipole interaction and cooperative effects ; K. Rustomji, M. Dubois, P. Jomin, S. Enoch, J. Wenger, C. Martijn de Sterke and R. Abdeddaim in Physical Review X, Vol 11 Issue 2

Contacts : Redha Abdedaïm, Stefan Enoch ou Jérôme Wenger

Financements : Ces travaux ont reçu des financements du programme de recherche et d’innovation Horizon 2020 de l’Union Européenne dans le cadre de la convention n°736937, de l’Agence Nationale de la Recherche (ANR) - subvention ANR-17-CE09-0026-01 et de l’Initiative d’Excellence d’Aix-Marseille Université - A*MIDEX, programme français «Investissements d’Avenir».

A lire également :
 Article sur le site internet de l’INSIS

Researchers Develop Laser-Based Process to 3D Print Detailed Glass Objects

Multiphoton polymerization approach might one day be used to print complex optics

Researchers Develop Laser-Based Process to 3D Print Detailed Glass Objects

We introduce a laser-based process relying on multi-photon induced polymerization to produce complex 3D glass parts. A focused, intense, laser beam is used to polymerize a transparent resin, loaded with additives and silica nanoparticles, at the wavelength of the laser beam through non-linear absorption processes. The object is created directly in the volume, overcoming the limitation of layer-by-layer process. The process enables the production of silica parts with consecutive debinding and sintering processes. 3D objects of centimetric dimensions are obtained with bulk silica density and a resolution that depends on the laser spot size.

Reference : "3D printing of silica glass through a multiphoton polymerization process", Thomas Doualle, Jean-Claude André and Laurent Gallais in Optics Letters Vol. 46, Issue 2, pp. 364-367 (2021)

Image Name : 3D printing a complex part

Caption : Researchers have developed a new laser-based process for 3D printing intricate parts made of glass. It uses multiphoton polymerization to create the object directly in a 3D volume.

Contact & Image Credit : Laurent Gallais, Institut Fresnel & Ecole Centrale Marseille

 News Release on, 12 January 2021 :

Other articles on our research :
 Article in OPN review, "A Laser-Based Process to 3D Print Glass", 29 January 2021 :
 Article in The Engineer "Multiphoton polymerisation creates 3D printed glass objects", 13 January 2021 :
 Article in The American Ceramic Society, "Laser-based process allows direct creation of 3D glass structures", 26 January 2021 :
 Article de la SATT-Sud Est "De la sculpture Optique pour révolutionner l’impression 3D", January 2021

"18F-FDG brain PET hypometabolism in patients with long COVID"

New publication in European Journal of Nuclear Medicine & Molecular Imaging

IMOTHEP Team of Institut Fresnel and IHU Méditerranée Infection - Marseille have just published an article in European Journal of Nuclear Medicine & Molecular Imaging.

In the context of the worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some patients report functional complaints after apparent recovery from COVID-19. This clinical presentation has been referred as “long COVID.” We here present a retrospective analysis of 18F-FDG brain PET of long COVID patients from the same center with a biologically confirmed diagnosis of SARS-CoV-2 infection and persistent functional complaints at least 3 weeks after the initial infection.

Methods : PET scans of 35 patients with long COVID were compared using whole-brain voxel-based analysis to a local database of 44 healthy subjects controlled for age and sex to characterize cerebral hypometabolism. The individual relevance of this metabolic profile was evaluated to classify patients and healthy subjects. Finally, the PET abnormalities were exploratory compared with the patients’ characteristics and functional complaints.

Figure : Brain 18F-FDG PET hypometabolism in patients with long COVID. In comparison to healthy subjects, the patients exhibit hypometabolism in the bilateral rectal/orbital gyrus, including the olfactory gyrus; the right temporal lobe, including the amygdala and the hippocampus, extending to the right thalamus; the bilateral pons/medulla brainstem; the bilateral cerebellum (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected; SPM8 3D rendering)

Results : In comparison to healthy subjects, patients with long COVID exhibited bilateral hypometabolism in the bilateral rectal/orbital gyrus, including the olfactory gyrus; the right temporal lobe, including the amygdala and the hippocampus, extending to the right thalamus; the bilateral pons/medulla brainstem; the bilateral cerebellum (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected). These metabolic clusters were highly discriminant to distinguish patients and healthy subjects (100% correct classification). These clusters of hypometabolism were significantly associated with more numerous functional complaints (brainstem and cerebellar clusters), and all associated with the occurrence of certain symptoms (hyposmia/anosmia, memory/cognitive impairment, pain and insomnia) (p < 0.05). In a more preliminary analysis, the metabolism of the frontal cluster which included the olfactory gyrus was worse in the 7 patients treated by ACE drugs for high blood pressure (p = 0.032), and better in the 3 patients that had used nasal decongestant spray at the infectious stage (p < 0.001).

Conclusion : This study demonstrates a profile of brain PET hypometabolism in long COVID patients with biologically confirmed SARS-CoV-2 and persistent functional complaints more than 3 weeks after the initial infection symptoms, involving the olfactory gyrus and connected limbic/paralimbic regions, extended to the brainstem and the cerebellum. These hypometabolisms are associated with patients’ symptoms, with a biomarker value to identify and potentially follow these patients. The hypometabolism of the frontal cluster, which included the olfactory gyrus, seems to be linked to ACE drugs in patients with high blood pressure, with also a better metabolism of this olfactory region in patients using nasal decongestant spray, suggesting a possible role of ACE receptors as an olfactory gateway for this neurotropism.

References :

  • 18F-FDG brain PET hypometabolism in patients with long COVID. Guedj E, Campion JY, Dudouet P, Kaphan E, Bregeon F, Tissot-Dupont H, Guis S, Barthelemy F, Habert P, Ceccaldi M, Million M, Raoult D, Cammilleri S, Eldin C. Eur J Nucl Med Mol Imaging. 2021 Jan 26:1-11. Doi: 10.1007/s00259-021-05215-4.
  • 18F-FDG brain PET hypometabolism in post-SARS-CoV-2 infection: substrate for persistent/delayed disorders ? Guedj E, Million M, Dudouet P, Tissot-Dupont H, Bregeon F, Cammilleri S, Raoult D. Eur J Nucl Med Mol Imaging. 2021 Feb;48(2):592-595. Doi: 10.1007/s00259-020-04973-x.

Affiliations : Aix Marseille Univ, APHM, CNRS, Centrale Marseille, Institut Fresnel, Hôpital de la Timone, CERIMED, Service de Médecine Nucléaire, Marseille, France

Partners : AMU, CNRS, Centrale Marseille, APHM, IHU, Institute Marseille Imaging, Institut Fresnel, IMOTHEP team, CERIMED, Service de Médecine Nucléaire, Hôpital Timone

Keywords : TEP, 18F-FDG, SARS-CoV-2, Coronavirus, Covid-19, Long COVID, anosmia, agueusie, fatigue, dysautonomie, douleur, dyspnée, plaintes cognitives, troubles de la mémoire, troubles de la concentration

Contact :

 Article in Le Monde February 18, 2021 "A Marseille, des pistes thérapeutiques pour les Covid longs"
 Article "Enquête sur les mystères du Covid long" in La Provence monday 8th february 2021
 Article "Covid-19 : vers la reconnaissance d’une forme longue chez les enfants" in Sciences & Avenir magazine of february 2021
 Chronicle on RTL radio on february 19, 2021 : Podcast on AP-HM website, in "Revue de Presse"
 Article "Covid-long: ce qui va changer pour les malades" in Notre Temps magazine of February 12, 2021
 Article "Covid long : les enfants et adolescents aussi sont touchés" on France Info TV February 16, 2021
 Chronicle Radio on France Info dans le 5h/7h du 16 février 2021 (Le billet Sciences) : Podcast on AP-HM website in "Revue de Presse"
 Reportages TV puis Interview de Brigitte Milhau sur le COVID long sur le 6/9 de CNews on february 17, 2021 - Replay from 02:10:30 to 2:15:04
 Reportage TV on France 3 Région in miday journal 12/13 du 17 février 2021

Première fabrication d’une fibre optique microstructurée en verre issue d’une préforme obtenue par impression 3D

Depuis la fabrication des premières fibres optiques microstructurées par Kaiser, Marcatili, et Miller in 1973, plusieurs techniques de fabrication de ces nouvelles fibres optiques ayant des sections transverses très variées ont été développées. C’est justement la grande variété possible de ces sections qui a permis le renforcement du contrôle de la propagation de la lumière dans ces nouvelles fibres. Si on se limite aux fibres en verres, on doit citer la plus connue et la plus utilisée des techniques de fabrication à savoir la méthode d’empilement et d’étirage, stack and draw and anglais, qui a permis de très nombreuses réalisations notamment à partir de verres de silice. Un autre exemple de technique est celle du moulage qui est utilisée surtout pour les verres spéciaux comme les verres de chalcogénure. Afin de permettre la fabrication de fibres avec des profils encore plus variés et donc d’obtenir un meilleur contrôle encore de la propagation de la lumière, il fallait pouvoir dépasser les limitations posées par les techniques actuellement disponibles. Pour atteindre cet objectif, une technique novatrice de fabrication par impression 3D de préforme de verres de chalcogénures a été développée. Elle a permis la fabrication d’une fibre optique microstructurée à coeur creux spécialement conçue pour l’infrarouge via la modélisation en tenant compte des contraintes de fabrication. Cette fibre a été caractérisée dans une large bande de l’infrarouge et les fenêtres de transmission observées sont correctement reproduites via l’utilisation de la théorie de modes couplés entre 7 et 9,6 µm. La conception et les modélisations des fibres ont été réalisées à l’Institut Fresnel via l’expertise acquises dans ce domaine depuis près de vingt ans. Ces travaux ouvrent la voie à la conception de nouveaux profils de fibres optiques microstructurées notamment en vue d’applications dans le domaine des capteurs, des lasers à fibres, et plus généralement du contrôle par fibre de la lumière dans l’infrarouge.

La préforme imprimée
(a) Vue schématique du design cible conçu à l’Institut Fresnel, chargée dans le logiciel de l’imprimante 3D customisée pour les verres de chalcogénures. (b) Section de la préforme de verre de chalcogénure TAS obtenue après l’impression 3D. (c) Vue de profil de la préforme réalisée avec une règle graduée pour l’échelle.
Courtoisie de l’ISCR de l’Université de Rennes.

Figure : La préforme imprimée: (a) Vue schématique du design cible conçu à l’Institut Fresnel, chargée dans le logiciel de l’imprimante 3D customisée pour les verres de chalcogénures. (b) Section de la préforme de verre de chalcogénure TAS obtenue après l’impression 3D. (c) Vue de profil de la préforme réalisée avec une règle graduée pour l’échelle.

Référence : "Mid-infrared hollow core fiber drawn from a 3D printed chalcogenide glass preform", J. Carcreff, F. Cheviré, E. Galdo, R. Lebullenger, A. Gautier, J.-L. Adam, D. Le Coq, L. Brilland, R. Chahal, G. Renversez and J. Troles - Optical Materials Express, vol 11 (1), pp. 198—209, (2021)

Financement : ANR et DGA (ASTRID DGA FOM-IR-2-20)

Contact : Prof. Gilles Renversez, Équipe Athena –

 Voir aussi ce lien sur site de l’Institut de Chimie du CNRS:

Ces travaux ont été réalisés par l’équipe Verres et Céramiques de l’Institut des Sciences Chimiques de Rennes (Univ. Rennes et CNRS), la société SelenOptics, et l’équipe Athena de l’Institut Fresnel (Univ. Aix-Marseille, CNRS, Centrale Marseille)

Machine learning allows a breakthrough in star birthplace studies

The current generation of receivers installed in the IRAM radio telescopes (30-meter antenna in the Sierra Nevada in Spain and NOEMA interferometer in the Plateau de Bure) brings millimetre radio astronomy into the era of massive data processing. These receivers can observe up to 240,000 different frequencies! Compared to the previous generation, the amount of data has been multiplied by a factor of about 50 and it will be again multiplied by the same factor with the next generation of receivers under development! This completely changes the way projects are conducted to meet the scientific challenges of astronomy.

An international team led by Jérôme Pety, Maryvonne Gerin, and Franck Le Petit obtained the most complete millimetre-wave observations of the Orion B cloud. This IRAM large program, named ORION-B (Outstanding Radio-Imaging of OrioN B), produced 240,000 images of 1100 x 750 pixels (enough data to make a 2h15 movie at 24 frames per second!).

© J. Pety/ORION-B Collaboration/IRAM

The Orion B cloud, known to house the Horsehead and Flame nebulae, is located just to the left of the hunter’s belt in the Orion constellation. The beautiful colors of the images of these two nebulae are due to the illumination of interstellar gas and dust by the intense ultraviolet radiation from the massive young stars nearby. The presence of such stars also explains the interest in this region among professional astronomers. Since the Orion cloud is one of the star-forming regions closest to us, it is possible to study in detail the birth mechanisms of massive stars and then how these will completely transform their birthplace.

These clouds, where stars are born, are complex systems. They involve the turbulent movements of gas, and numerous processes that link the different scales of the cloud, from the nanometric scale of the molecules to the scale of the cloud as a whole (tens of light years). This is also the place of a chemical evolution that gradually leads to increasingly complex molecules (such as methanol, glycol-aldehyde). Jérôme Pety comments: "Faced with a system of such complexity, subject to the vagaries of its environment and history, a complete causal and deterministic understanding is no longer possible. We must now seek to understand the evolution of such clouds towards the formation of new stars and their planets in the form of statistical laws (i.e. which apply on average to a large number of observations). The ORION-B project has precisely the enormous amount of data needed to identify these statistical laws. Its goal is therefore to build this new statistical vision of the evolution of the interstellar medium and star formation. With the help of statisticians, it is necessary to find out how to extract the laws from the huge amount of observed data. In particular, this involves machine learning algorithms (the engine behind the current revolution in artificial intelligence) that can extract the regular behaviors from it.”

The first analyses of the ORION-B data in 2017 and 2018 had highlighted the qualitative links between the emission of the molecules (what we observe) and the physical conditions of the environment that emits (amount of matter present, density of the gas, amount of UV rays received by the cloud, ...). These results had already been noticed by the astronomical community as attested by a viewpoint published in the journal Nature (Wiseman & Sewilo, Nature, 2017, 546, p.37-39). To go further and derive quantitative relationships between observations and physical quantities, the team has joined forces with four groups of statisticians in France (Grenoble, Lille, Marseille, Nantes), and it is the first results of this collaboration that appear today, in a series of three articles.

The first of these works addresses a recurring problem. The main constituent of molecular clouds, namely molecular hydrogen, is invisible at the very low temperatures (-250°C) of the interstellar medium. These clouds can therefore only be studied using minority tracers such as dust (which emits in infrared) or other molecules present in the trace state (which emit radio waves). The most commonly used tracer is carbon monoxide, whose average concentration is about one molecule per 10,000 hydrogen molecules. When used alone, it provides only a very imprecise estimate of the amount of gas. The idea of combining it with other observable chemical species has often been explored, but the complexity of the physico-chemical relationships involved makes the task difficult. Bordeaux researcher Pierre Gratier has tackled this problem with a new approach. Pierre Gratier says: "We have shown that a machine learning algorithm ("random forests") can reveal, and thus help us understand the relationship that binds the different observable molecules to the total quantity of gas. It is thus possible to build a reliable and precise estimator of the quantity of hydrogen from the emission of a reduced set (between 5 and 10) of different tracers".

Emission du monoxyde de carbone dans le nuage Orion B
© J. Pety/ORION-B Collaboration/IRAM

Beyond observations, the models become so massive and complex that it is now impossible to notice the interesting regularities with a “naked eye". Modelers work tirelessly to complete computer simulations, gathering one after the other, the many elementary physical and chemical processes that govern these clouds. Faced with the complexity that emerges when combining all these elementary laws, the full range of possible scenarios must be systematically explored (different cloud densities and temperatures, UV fields from more or less nearby stars, etc). Modellers thus amass countless model results, for which extracting the relationships between the different parameters of the studied scenario and the observable quantities becomes inextricable by hand. Emeric Bron, a researcher at the Paris Observatory, has shown how a machine learning approach can be used to automatically process this huge quantity of models to answer a riddle that modelers have been facing for three decades: Among all the molecular lines that we can try to observe, which ones will give us the most information about the parameters that describe the real state of the gas that emits these lines. Emeric Bron was particularly interested in the fraction of free electrons present in the gas (or ionization fraction). Emeric Bron specifies: "The existence of a small fraction of electrons and ions in the gas is indeed crucial for its evolution. On the one hand, the gas becomes sensitive to the presence of the cloud’s global magnetic field, which will channel its movements during the gravitational collapse that forms stars. On the other hand, the ions allow much faster chemical reactions, thanks to an electromagnetic attraction at a greater distance with the other reagents. They thus make it possible to initiate interstellar chemistry down to complex organic molecules. Our results indicate to observers which molecular lines are sensitive to the electron fraction. This will allow astronomers to understand quantitatively how the chemistry of the medium leads to complex organic molecules or how the magnetic field controls the gravitational collapse into stars".

Finally, comparing models with observed data faces an additional challenge: observations are imperfect. Even if it is considered as close, the Orion B cloud remains at a very large distance, and the received radio emission is quite faint. When trying to interpret these data using physical models, the noise they contain can blur the conclusions. In a third study, Marseille-based statistician Antoine Roueff quantifies precisely whether/how observations may reliably answer the questions astronomers ask themselves, and the minimum observation time (noise decreases with longer observations) to do this. Antoine Roueff says "By applying this method to carbon monoxide observations, it is possible to separate the physical information from the artifacts caused by noise. This sheds new light on the results obtained in the first article of this series, beginning to understand the physics that explains how minority molecules can be reliably used to estimate the total amount of hydrogen".

ORION-B project website: pety/ORION-B

Contact at Fresnel : Antoine ROUEFF, équipe PHYTI

Contact Press : François Maginiot, Attaché de presse CNRS,

References :

  • Quantitative inference of the H2 column densities from 3mm molecular emission: A case study towards Orion B. Pierre Gratier, Jérôme Pety, Emeric Bron, Antoine Roueff, Jan H. Orkisz, Maryvonne Gerin, Victor de Souza Magalhaes, Mathilde Gaudel, Maxime Vono, Sébastien Bardeau, Jocelyn Chanussot, Pierre Chainais, Javier R. Goicoechea, Viviana V. Guzmán, Annie Hughes, Jouni Kainulainen, David Languignon, Jacques Le Bourlot, Franck Le Petit, François Levrier, Harvey Liszt, Nicolas Peretto, Evelyne Roueff, et Albrecht Sievers. A&A, le 19 novembre 2020.
  • Tracers of the ionization fraction in dense and translucent gas: I. Automated exploitation of massive astrochemical model grids. Emeric Bron, Evelyne Roueff, Maryvonne Gerin, Jérôme Pety, Pierre Gratier, Franck Le Petit, VivianaGuzman, Jan H. Orkisz, Victor de Souza Magalhaes, Mathilde Gaudel, Maxime Vono, Sébastien Bardeau, PierreChainais, Javier R.Goicoechea, Annie Hughes, Jouni Kainulainen, David Languignon, Jacques Le Bourlot,François Levrier, Harvey Liszt, Karin Öberg, Nicolas Peretto, Antoine Roueff et Albrecht Sievers. A&A, le 19 novembre 2020.
  • C18O, 13CO, and 12CO abundances and excitation temperatures in the Orion B molecular cloud : An analysis of the precision achievable when modeling spectral line within the Local Thermodynamic Equilibrium approximation. Antoine Roueff, Maryvonne Gerin, Pierre Gratier, François Levrier, Jérôme Pety, Mathilde Gaudel, Javier R.Goicoechea, Jan H. Orkisz, Victor de Souza Magalhaes, Maxime Vono, Sébastien Bardeau, Emeric Bron, Jocelyn Chanussot, Pierre Chainais, Viviana V. Guzman, Annie Hughes, Jouni Kainulainen, David Languignon, Jacques Le Bourlot, Franck Le Petit, Harvey S. Liszt, Antoine Marchal Marc-Antoine Miville-Deschênes, Nicolas Peretto, Evelyne Roueff et Albrecht Sievers. A&A, le 19 novembre 2020.

● Discover the IRAM 30 meter telescope !
● Beyond the appearances: The anatomy of the Orion Jedi revealed by radio-astronomy.
● Filaments around the Horsehead Nebula are still too young to form stars.
● Zooming intothe skin of the Orion hunter
● Article over Orion-B "Machine learning: a breakthrough in the study of stellar nurseries" in the Press Area of CNRS France

Study of an analogue of the Itokawa asteroid in the field of microwave electromagnetic waves

The small bodies of the solar system (asteroid comets), and especially their internal structures, are still poorly known. Knowledge of the interior of comets and asteroids could provide important information about their formation process, but also about the early solar system. In this paper, we have studied the possibility of obtaining this kind of information from their response to an incident electromagnetic wave.
This study focused on an analogue of asteroid 25143 Itokawa, which is a small asteroid "visited" by the Hayabusa mission of the Japanese Space Agency (JAXA) in 2005.

Figure 1: Analogue de l’astéroïde Itokawa

Measurements in an anechoic chamber, in the microwave range, were carried out to simulate in a controlled environment a space mission carrying a radar. Two "full wave" models, one of them
in the frequency domain and the other in the time domain, were applied to describe the interaction of the incident wave with this analogue.
Comparisons between modelling and laboratory measurements make it possible to distinguish the signature of the internal structure of the analogue and demonstrate the interest of a radar inspection of such celestial bodies. The results also show that a full wave modelling taking into account not only the first order but also the multiple diffraction is necessary here.

This study was carried out as a collaboration between researchers from the Department of Mathematics and Statistics of the University of Tampere and researchers from the Fresnel Institute.

Figure 2: Configuration de mesures de la signature radar d’un analogue d’astéroïde

Reference : C. Eyraud, L.-I. Sorsa, J.-M. Geffrin, M. Takala, G. Henry, S. Pursiainen, Full Wavefield Simulation versus Measurement of Microwave Scattering by a Complex 3D-Printed Asteroid Analogue, Astronomy & Atrophysics, in press,

 Link toward the scientific article in open access

Contact : Christelle Eyraud, Research Group HIPE

Première mise en évidence des ondes non-linéaires auto-confinées au sein de structures plasmoniques

Prédites depuis plus de quarante ans par des études théoriques russes et américaines, ces ondes ont enfin été mises en évidence et étudiées. Ces ondes, dont les plasmons-solitons sont le cas particulier se propageant de manière auto-cohérente, ont connu un fort regain d’intérêt durant les deux dernières décennies avec le développement de la plasmonique. Ainsi de très nombreux travaux théoriques et numériques notamment ceux réalisées à l’Institut Fresnel les ont exploré mais ces ondes non-linéaires n’avaient jusqu’à maintenant jamais été observées expérimentalement.
Ces ondes non-linéaires de surface se propagent dans une structure plasmonique planaire où la nonlinéairité est assurée par un verre présentant à la fois une forte non-linéarité Kerr optique (plusieurs centaines de fois celle de la silice) et une faible photo-sensibilité. Les observations n’ont été rendues possible que par les remarquables caractéristiques de ce verre de chalcogénure, par la conception d’une structure optimisée par des simulations numériques préalables utilisant une nouvelle méthode de détermination des solutions non-linéaires, et par la longue expertise expérimentale acquise précédemment dans l’étude des solitons spatiaux.
Afin de rendre compte des résultats expérimentaux, une version améliorée de l’équation de Schrôdinger non-linéaire spatiale a notamment été développée afin de prendre en compte correctement les propriétés des ondes se propageant sous la partie métallique de la structure. Des comparaisons expériences/simulations ont ainsi pu être réalisées avec un accord qualitatif et quantitatif.
Cette mise en évidence de ces ondes non-linéaires auto-confinées au sein de structures plasmoniques ouvre la voie à leur utilisation dans des applications en plasmonique non-linéaire intégrée en effet de très fortes focalisations peuvent être générées sur des distances de quelques dizaines de micromètres et à des puissances raisonnables.


Figure : Schéma de principe de l’expérience avec un motif en or situé sur la partie supérieure de la structure planaire contenant la couche de verre hautement non-linéaire.

Référence : "Nonlinear Self-Confined Plasmonic Beams: Experimental Proof", Tintu Kuriakose, Gilles Renversez, Virginie Nazabal, Mahmoud M. R. Elsawy, Nathalie Coulon, Petr Němec, and Mathieu Chauvet, ACS Photonics (2020).

Contact : Prof. Gilles Renversez, Equipe Athena, –

Ces travaux ont été publiés dans la revue ACS Photonics.
Le projet est issu de l’institut Fresnel (Univ. Aix-Marseille, CNRS, Centrale Marseille) qui a réalisé le design des structures et leur modélisation. Leur fabrication a été assurée par l’ISCR (Univ. de Rennes I, CNRS), et l’ITER (Univ. de Rennes I, CNRS) ainsi que par l’université de Pardubice en république Tchèque. Les caractérisations optiques ont été effectuées au sein du département de photonique de l’institut FEMTO-ST (Univ. de Bourgogne Franche-Comté, CNRS).

 Article mis en ligne sur le site de l’INSIS dans la rubrique «Actualités scientifiques» : Une première mise en évidence des ondes non-linéaires autoconfinées au sein de structures plasmoniques

Arago’s spot generated in the time domain in an optical fiber

Bicentenary of Augustin Fresnel’s work

When light encounters an obstacle in its path, it can behave in a way that is incompatible with the simple geometric laws of reflection and refraction. Augustin Fresnel’s theory of light diffraction was a turning point in the fine understanding of the paradoxical behavior of light waves. In 1819, his fundamental thesis was awarded the Grand Prix des sciences mathématiques launched by the Académie des Sciences. His work did not immediately reach consensus and gave rise to bitter debates, particularly between Siméon Poisson, who was not in favor of Fresnel’s vision, and François Arago, a physicist but also the future French Prime Minister. The unintuitive observation of a bright spot in the shadow of an opaque circular object allowed a definitive decision to be made in favor of the ideas put forward by Fresnel. This task has remained in history as the Fresnel or Arago task.

However, the diffraction that affects the spatial behavior of the light wave has an exact temporal equivalent: dispersion. Thus, when a light wave encounters a temporal obstacle, it will exhibit a behavior similar to diffraction. We have been able to take advantage of this time-space duality in several experiments carried out in optical fibers to synthesize time gratings [1] or to reinterpret interference phenomena in the time domain, such as those obtained by Fresnel or Félix Billet, former dean of the Faculty of Science in Dijon[2].

As part of the bicentenary of Fresnel’s work, a collaborative project between the Institut Fresnel and the Carnot Interdisciplinary Institute of Burgundy enabled us to recreate, still using optical fibers, the time analogue of Arago’s task. By exploiting all the possibilities of fine temporal characterization of the PICASSO platform of the CARNOT Interdisciplinary Laboratory of Burgundy, we were able to highlight the emergence of a luminous peak where initially there was only darkness [3]. We have also highlighted the influence of light power on these light structures.

Contact :
 Pr. Christophe FINOT,

More Information :
 [1] - C. Finot, H. Rigneault, Experimental observation of temporal dispersion gratings in fiber optics, Journal of the Optical Society of America B, 2017, 34 p 1511
 [2] F. Chaussard, H. Rigneault, C. Finot, Two-wave interferences space-time duality: Young slits, Fresnel biprism and Billet bilens, Optics Communications, 2017, 397, 31.
 [3] C. Finot, H. Rigneault, Arago spot formation in the time domain, Journal of Optics 21, 105504 (2019).

Ceramic resonators offer new possibilities for magnetic resonance microscopy

Systematic Analysis of the Improvements in Magnetic Resonance Microscopy with Ferroelectric Composite Ceramics

Magnetic Resonance Microscopy enables imaging of samples in the millimetre domain with sub-micrometric resolution. We developed a new type of probe made of ceramic material allowing to produce images with resolution twice higher than with conventional metal probes.

Amélioration du RSB lors de l’imagerie d’un échantillon de houx.
A gauche, représentation schématique du champ magnétique généré par chaque sonde.
Au milieu, distribution du champ magnétique dans une coupe sagittale, estimée par simulation numérique.
A droite, image obtenue par MRM de l’échantillon de houx.
© ITMO-Institut Fresnel-Multiwave-CEA

In magnetic resonance microscopy (MRM), an imaging modality that focuses on imaging of samples of a few millimetres size, the commonly used probe is a solenoid coil made of copper wire. When fed by an electrical current, it produces a magnetic field which is essential to obtain an image. Doing so, an electric field is also generated within the biological sample. The latter usually being conductive, it induces dielectric losses and represents a source of noise. At fixed acquisition time, this phenomenon intrinsically limits the achievable signal-to-noise ratio (SNR) and, therefore, the resolution.
In this framework, several research works have evoked and demonstrated the potential of ceramic probes to overcome this limitation at several static magnetic field intensities B0. These probes exploit the first transverse electric mode of an annular-ring dielectric resonator which is simply excited by a small current loop. Among the special features of this resonator are its axial magnetic field, similar to that of the reference probe, together with an insignificant electric field. The resonator properties are chosen so that the mode of interest resonates at a frequency close to the Larmor frequency of protons at the given B0 field intensity. At 17 T, the studied resonator had to be made of a ceramic with relative permittivity 530 while ensuring a low intrinsic loss level within the dielectric material to avoid additional noise during the MRI acquisition. These constraints – high permittivity and low losses – could be relieved with a customised new ferroelectric ceramic material containing magnesium additives.
A semi-analytical model was set up to propose an estimation of the achievable SNR. This allowed to compare the performances of the ceramic probe with the solenoid coil as a parametric estimation problem depending on the electromagnetic properties of both the ferroelectric material and the sample. Numerical simulations validated this approach in the studied configuration that was also experimentally tested for imaging of vegetal sample (ilex aquifolium) at 17 T.
Experimental investigations in MRI confirmed predictions of the theoretical and numerical studies, that is an SNR gain of around 2 in favour of the ceramic probe over the solenoid coil. This was explained by the very limited electric field – sample interaction in the case of ceramic probe, thanks to the electric field distribution presenting remarkably low values in the sample region.
This research paves the way for a novel approach of microscopy probes development. Optimized designs of ceramic probes are enabled by the opportunity to elaborate customized ferroelectric materials. For a sample with given dimensions and properties, it has become possible to make an informed decision about choosing a solenoid coil or a ceramic probe in order to reach the best image resolution

Partners :
 CEA NEUROSPIN - Read the article of CEA Joliot Curie
 ITMO University

Reference : M. A.C. Moussu, L. Ciobanu, S. Kurdjumov, E. Nenasheva, B. Djemai, M. Dubois, A. Webb, S. Enoch, P. Belov, R. Abdeddaim, S. Glybovski, “Systematic Analysis of the Improvements in Magnetic Resonance Microscopy with Ferroelectric Composite Ceramics”, accepted for publication in Advanced Materials
Version of Record online : 17 May 2019

 CNRS INSIS also published this information in his newsletter "En direct des labos" under the title "Une antenne en céramique améliore la qualité des images par résonance magnétique"

Contacts :
Marine Moussu, Institut Fresnel - UMR7249, Marseille
Luisa Ciobanu, CEA Neurospin, Gif-sur-Ivette
Stanislav Glybovski, ITMO University, Saint-Pétersbourg

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement n°736937

Toward an ever-more efficient collaboration between academia and industry

Angularly tunable bandpass filter: design, fabrication and characterization

Thin-Film filters offer a wide range of applications from earth observation to biophotonics. They are generally hidden components in systems but play a key role in improving the performances of optical instruments. Recent collaborative efforts between the Thin-Film research team of Institut Fresnel and Bühler company have permitted to demonstrate new high performance angularly tunable filter for near-infrared range. This filter, composed with a total of about 300 layers has been successfully designed and fabricated on a Bühler HELIOS machine (Plasma Assisted Reactive Magnetron Sputtering) combined with Optical Monitoring System. A custom dedicated measurement setup has also been developed in order to measure the performances of this high performance optical filter. Close to theoretical performances of this class of filter has been demonstrated. These results not only highlight the capability to develop complex filters within the Espace Photonique platform at Institut Fresnel, but also a very fruitful collaboration between Academia (Institut Fresnel) and industry (Bühler company) for the development of optical components with more and more ultimate performances.

Image : Left – Measured and theoretical transmission spectral performances of the fabricated filter / Right – Illustration of optical interference filters

Reference :
J. Lumeau, F. Lemarchand, T. Begou, D. Arhilger, and H. Hagedorn, "Angularly tunable bandpass filter: design, fabrication and characterization", Optics Letters 44(7), 1829-1832 (2019) – Editors’ Pick.

More Informations:
 on our Photonic Space, "Plateforme Technologique d’Aix Marseille Université"
 on our partner BUHLER

Contact : Julien Lumeau

Imaging energy transfer between dipole antennas inside a photonic cavity

Photonic cavities provide a way to enhance interactions between dipoles. A new theoretical and experimental analysis provides design rules for optimizing this enhancement at microwave frequencies.

Light can be trapped inside a cavity made by two mirrors, thus concentrating the light intensity and enhancing interactions between light and matter. Among the different applications of these photonic cavities, much attention is now focused on their ability to control the energy exchange between quantum emitters such as atoms, molecules, and quantum dots. Attempts to improve this exchange have been hampered by experimental difficulties in controlling the positions, orientations, and spectra of the emitter’s dipoles. Here, we thoroughly characterize dipole-dipole energy transfer inside a photonic cavity, and provide design rules for cavity-enhanced applications.

At the nanoscale, the energy transfer between two light-sensitive elements is primarily governed by a dipole-dipole interaction described by a mathematical formalism known as Förster resonance energy transfer (FRET). We developed a general methodology to analyze FRET at microwave frequencies. While previous research has focused on optical frequencies, microwave experiments allow us to measure energy transfer with a high degree of control over dipole orientation and position. We then test our framework by investigating the energy transfer between two microwave antennas inside a photonic cavity and derived the conditions that enhance the transfer.

Our methodology bridges the gap between quantum electrodynamics and microwave engineering descriptions of dipole-dipole interactions. Beyond the conceptual interest, this approach provides a practical tool to quantitatively characterize photonic devices with an enhanced dipole-dipole interaction and can be readily applied to map energy transfer inside complex photonic systems at ultrahigh resolutions.

Direct measurement of the energy transfer between dipole antennas inside a photonic cavity.

This research was conducted within the context of the International Associated Laboratory “ALPhFA: Associated Laboratory for Photonics between France and Australia”, and has received funding from the European Union’s Horizon 2020 Research and Innovation programme under Grant Agreement No 736937, from the Agence Nationale de la Recherche (ANR) under grant agreement ANR-17-CE09-0026-01, and from Excellence Initiative of Aix-Marseille University - A*MIDEX, a French “Investissements d’Avenir” program.

 Read the article on the CNRS - INSIS website :
« Une cartographie des transferts d’énergie dans les cavités optiques radiofréquences »

K. Rustomji, M. Dubois, B. Kuhlmey, C. M. de Sterke, S. Enoch, R. Abdeddaim, J. Wenger, “Direct imaging of the energy transfer enhancement between two dipoles in a photonic cavity”, Physical Review X , march 2019

Contact: Redha Abdeddaim, Stefan Enoch and Jérôme Wenger

Metamaterial enhanced ultra-high field magnetic resonance imaging

A team of physicists from our Lab, the Langevin Institute and the CEA NeuroSpin recently published in the prestigious Physics Review X their work on Metamaterials to improve the quality of ultra-high field magnetic resonance imaging (MRI 7T).

Novel metamaterial approach improves image quality of magnetic resonance imaging obtained with ultra-high magnetic field scanners. This approach helps to advance these cutting-edge equipment towards global clinical applications for faster and more precise medical imaging.

Since its discovery in the early 70’s, MRI scanners have become one of the most efficient diagnostic tools available for physicians. Also, over time, their magnetic field strength has been steadily increased to enhance the Signal to Noise Ratio yielding a radical improvement of spatial and temporal resolution as well as biological contrast. On the other hand, such a strategy induces an increasing working frequency of the radio-frequency (RF) excitation field. It becomes problematic as human body size becomes non negligible compared with the associated wavelength. This induces strong RF field inhomogeneities leading to major losses in contrast or shadowing on the images and strongly limits the clinical application of High-Field MRI scanners.

The M-Cube project breakthrough is based on electromagnetic metamaterials offering an unprecedented ability to tailor RF field inside MRI coils. The interaction of electromagnetic modes within the metamaterial enables the access to the so-called Kerker scattering conditions leading to either a 3-fold enhancement of the local RF field or to be used as a local RF shield in order to protect over exposed body areas

Reference: “Kerker effect in ultrahigh-field magnetic resonance imaging” ; Marc Dubois, Lisa Leroi, Zo Raolison, Redha Abdeddaim, Tryfon Antonakakis, Julien de Rosny, Alexandre Vignaud, Pierre Sabouroux, Elodie Georget, Benoit Larrat, Gérard Tayeb, Nicolas Bonod, Alexis Amadon, Franck Mauconduit, Cyril Poupon, Denis Le Bihan, and Stefan Enoch; Phys. Rev. X


Labs concerned by this article:
 Institut Fresnel
 Institut Langevin
 CEA NeuroSpin

Contact Researcher: Redha Abdeddaim, Stefan Enoch et Marc Dubois

This work is part of the H2020 FET-Open M-Cube project. It has received funding from the European Union’s Horizon 2020 Research and Innovation program under Grant Agreement No 736937


Correlated Disordered Plasmonic Nanostructures Arrays for Augmented Reality

The optical properties of metallic nanoparticles are exploited to design transparent surfaces used in innovative display devices. The subwavelength characteristic dimensions of nanoparticles are optimized to obtain a reflection efficiency at the desired color without altering the overall transparency quality of the substrate. Their spatial arrangement is chosen to eliminate non-specular diffraction, regardless of their spatial density. The responses of different silver nanoparticle arrangements (periodic or correlated-disordered arrangements, different spatial densities and nanoparticle dimensions) are analyzed numerically and experimentally by measuring the reflectance and transmittance spectra in the visible. It is shown that correlated-disordered arrangements decrease the effect of non-specular diffraction occurring at low spatial densities of nanoparticles. This low density of nanoparticles makes it possible to obtain a better overall transparency of the device. These configurations are promising for the design of innovative display devices of interest to the transport industry (e. g. head-up vision in the automobile) or "augmented reality" applications.

 Centre de Nanosciences et de Nanotechnologies, CNRS / Université Paris-Sud
 Institut Fresnel, CNRS / Université d’Aix-Marseille / Centrale Marseille
 Groupe PSA

Reference: "Correlated Disordered Plasmonic Nanostructures Arrays for Augmented Reality", Hervé Bertin, Yoann Brûlé, Giovanni Magno, Thomas Lopez, Philippe Gogol, Laetitia Pradere, Boris Gralak, David Barat, Guillaume Demésy and Beatrice Dagens. ACS Photonics, 2018, 5 (7), pp 2661–2668,

DOI: 10.1021/acsphotonics.8b00168

Keywords : nanosciences, optics, metasurface, augmented reality

Contact Institut Fresnel : Boris Gralak or Guillaume Demésy

Contact Centre de nanosciences et de nanotechnologies : Béatrice Dagens

Other publications on this subject:
La lettre de l’innovation du CNRS, n°45, Ajuster la réflectance d’un verre tout en préservant sa qualité de transparence

Long-range correlations measured between water molecules

The configuration of water molecules in an aqueous solution transitions from a long-range stacked pattern to a short-range radial pattern when salt is added.

In this article, published in the journal Physical Review Letters, Julien Duboisset (Institut Fresnel, Marseille) and Pierre-François Brevet (Institut Lumière Matière, Lyon) describe nonlinear optical experiments in the liquid phase determining the orientation correlation of water molecules. These experiments show that water molecules are organized over much greater distances than is usually accepted. They demonstrate indeed that the molecules are orientationnally arranged over distances of several tens of nanometers in a spatial azimuthal distribution. This work also show that when salt is added, a transition occurs where water molecules abruptly change their initial organisation into a short scale radial distribution centered on the salt ions.
This discovery, published in the journal Physical Review Letters and selected by the editor as a highlight, challenges the classic view of liquids and their organization of molecules at the nanoscale.

Left : Illustration of long range correlations between water molecules. In red, water molecules, in blue salts.
Right : lenght of correlations as function of salt concentration.

Reference :
Salt-induced Long-to-Short Range Orientational Transition in Water, Julien Duboisset and Pierre-François Brevet, Phys. Rev. Lett. 120, 263001 (2018) - Consulter l’article on-line

Contact Researchers :

 Julien Duboisset, Institut Fresnel - UMR7249, Aix Marseille Univ, CNRS, Centrale Marseille, 13013 Marseille, France (INSIS)
Tél : 04 91 28 80 49

 Pierre-François Brevet, Institut Lumière Matière – UMR 5306, Université Lyon1, CNRS, 69622 Villeurbanne, France (INP)

"Enhancing magnetic light emission with all-dialectric optical nanoantennas"

Article published in Nano Letters, september 2018

Des chercheurs ont élaboré une nanostructure capable d’accroître le champ magnétique d’une onde lumineuse, ouvrant la possibilité d’observer l’interaction entre cette composante magnétique de la lumière, et la matière.

Ces travaux ont été menés par des physiciens de l’Institut des nanosciences de Paris (CNRS/Sorbonne Université) et l’Institut de Ciencies Fotoniques, en collaboration avec :
 le Laboratoire de physique et d’études des matériaux (CNRS/ESPCI Paris/Sorbonne Université),
 l’IBM Almaden Research Center (USA),
 l’Institut Fresnel (CNRS/AMU/Centrale Marseille),
 le Laboratoire de physique de la matière condensée (CNRS/X
 l’Institut Langevin (CNRS/ESPCI Paris/Univ. Paris Diderot/Inserm/Sorbonne Université)

Enhancing magnetic light emission with all-dielectric optical nanoantennas
M. Sanz-Paz, C. Ernandes, J. Uriel Esparza, G. W. Burr, N. F. van Hulst, A. Maitre, L. Aigouy, T. Gacoin, N. Bonod, M. F. Garcia-Parajo , S. Bidault et M. Mivelle,
Nano Letters (2018)

Développement d’un technique d’imagerie moléculaire des tissus pour des applications médicales "SRGold"
Projet de maturation de la SATT Sud-Est en collaboration avec le CNRS et HORIBA France

Grâce à une avancée majeure en microscopie Raman stimulée, des chercheurs de l’équipe MOSAIC proposent désormais de réaliser en quelques minutes une image des molécules présentes dans un échantillon biologique. Les perspectives sont donc de pouvoir produire une nouvelle génération d’instruments hospitaliers afin de mieux identifier les tissus cancéreux.

La technique de Spectroscopie Raman Stimulée (SRS) permet de localiser dans un échantillon certaines espèces chimiques, identifiées par le type de liaisons qu’elles contiennent. Cette méthode appliquée à la microscopie de tissus biologiques permettra notamment de distinguer les tissus qui ont un caractère cancéreux. Or, les signaux Raman des molécules recherchées (collagène, acides aminés, ADN...) sont faibles et masqués par des signaux parasites. Des chercheurs de notre laboratoire ont donc résolu ces difficultés en améliorant le dispositif de microscopie SRS.

Baptisé SRGold pour "Stimulated raman gain opposite loss detection", ce système breveté en copropriété entre le CNRS et Aix Marseille Université (AMU) a pour effet d’annuler les signaux parasites, tout en multipliant par deux l’intensité du signal des molécules recherchées dans un tissu. Ces résultats sont obtenus grâce à un troisième faisceau laser, qui s’ajoute aux deux lasers qui équipent déjà un dispositif SRS traditionnel.

Le projet de maturation de la SATT Sud-Est, en collaboration avec le CNRS, a pour objectif de montrer l’apport de la technologie SRGold dans un contexte hospitalier. Ce projet est mené en collaboration avec l’Institut Paoli-Calmettes pour la détection de cancers du tube digestif et avec l’Hôpital de la Timone pour la détection de tumeurs cérébrales.

La technologie SRGold devrait permettre d’obtenir des images d’histologie moléculaire d’un tissu cancéreux en quelques minutes, au lieu de 24 heures avec l’histologie standard, et sans avoir recours à aucun marqueur explique Hervé Rigneault, responsable de l’équipe MOSAIC à l’origine de ce projet.

La société HORIBA France est enfin partenaire de ce projet de maturation, qui débouchera sur une licence d’exploitation exclusive concédée par la SATT Sud-Est. A plus long terme, la technologie SRGold étant adaptable à une fibre optique, des applications à l’endoscopie devraient également être envisagées.

Contact : Hervé RIGNEAULT

On the scattering directionality of a dielectric particle dimer of High Refractive Index

"Open access" Article on

Low-losses and directionality effects exhibited by High Refractive Index Dielectric particles make them attractive for applications where radiation direction control is relevant. For instance, isolated metallo-dielectric core-shell particles or aggregates (dimers) of High Refractive Index Dielectric particles have been proposed for building operational switching devices. Also, the possibility of using isolated High Refractive Index Dielectric particles for optimizing solar cells performance has been explored. Here, we present experimental evidence in the microwave range, that a High Refractive Index Dielectric dimer of spherical particles is more efficient for redirecting the incident radiation in the forward direction than the isolated case. In fact, we report two spectral regions in the dipolar spectral range where the incident intensity is mostly scattered in the forward direction. They correspond to the Zero-Backward condition (also observed for isolated particles) and to a new condition, denoted as “near Zero-Backward” condition, which comes from the interaction effects between the particles. The proposed configuration has implications in solar energy harvesting devices and in radiation guiding.

Two particles to scatter the energy in the forward direction when a single particle behaves as a reflector

Revealing the crystalline details of a biomineral shell structure
Towards the understanding of biomineralization thanks to a new x-ray microscopy

Biomineralization processes, which produce outstandingly complex mineralized structures in living organisms, are still poorly understood. Thanks to 3D Bragg ptychography, a recently proposed x-ray microscopy, new structural features of a paradigmatic calcareous biomineral have been revealed, allowing supporting recently proposed biomineralization models [1].

In many living organisms, biomineralization processes regulate the production of the mineralized tissues such as bones, teeth, shells… Deciphering these mechanisms is of crucial importance for materials science, as it will provide bio-inspired strategies for the synthesis of nanostructured inorganic materials using soft chemistry and environmentally friendly processes. Strong impacts are also expected in paleoclimatology that uses biomineral proxies to perform paleoclimate reconstructions. Among the existing biominerals, calcium carbonate biomineral is one of the most striking examples: while it is clear that theories arising from classical crystallization (involving monomer-by-monomer addition) can not explain the production of highly regulated calcareous crystalline biomineral structures as the ones observed in sea urchin or pearl oyster, for instance, the production of this major constituent of the Earth’s crust is still poorly understood.

The present study developed by an interdisciplinary French team lead by Institut Fresnel was motivated by an apparent contradiction observed in biomineral structures: while calcareous crystallizing species present a remarkable architectural diversity at the macro and micro-scales, their sub-micrometric scale is characterized by the consistent observation of a granular, but crystalline, structure. Hence, a proper description of the crystalline features at this mesoscale level, i.e., over a few sub-micrometric (50-500nm) granules, is a key to building realistic scenarios of biomineralization. However, none of the currently used experimental approaches (electron- or x-ray-based diffraction microscopies) is able to provide access to the detailed 3D crystalline granule arrangement.

In 2011, scientists from Institut Fresnel have proposed a new approach, named Bragg ptychography, to image in 3D the crystalline properties of complex materials [2]. This cutting-edge synchrotron-based x-ray microscopy was implemented at a synchrotron source (ESRF-ID13 beamline) and used to reveal the details of the mesocrystalline organization in calcite prisms, the generic mineral units of the pearl oyster shell (Figure). While these prisms are usually described as single-crystal, the 3D image proves the existence of large iso-oriented and iso-strained crystalline domains, slightly different one from the other (Figure). These original results call for specific non-classical crystallization pathways: the highlighted mesocrystalline properties support recent biomineralization models, involving partial fusion of oriented attached nanoparticle assembly and/or liquid droplet precursors.

This study has been performed in the framework of a 4-year ANR grant. It constitutes the starting point of an ERC project, aiming at defining the physical, chemical and biological conditions needed to produce synthetic biominerals, on demand. We expect that the unique properties of the forthcoming synchrotron sources combined to the new (and fast) Bragg ptychography microscopy [3] will enable them to achieve this goal.

Figure : Image tridimensionnelle des propriétés cristallines d’un prisme cristallin constituant la coquille d’une huitre perlière. (A) L’huitre perlière et (B) sa structure prismatique en bord de coquille. (C) La zone sondée (en jaune) à l’intérieur d’un prisme. Mise en évidence de domaines de rotations (D) et déformations (E) à l’intérieur du biominéral « mono-cristallin », Adaptée de F. Mastropietro et al., Nature Materials (2017).

Figure: 3D image of the crystalline properties of a biomineral. (A) Optical image of the investigated pearl oyster shell (Pinctada margaritifera) highlighting the investigated region (white rectangle). (B) Zoom-in view of the shell border showing its microscopic structure, composed of juxtaposed calcite prisms. (C) The probed volume (in yellow-grey) represents a small portion of a whole prism. (D) 3D Rotation and (E) strain maps, showing the existence of crystalline domains within the “single-crystalline” like biomineral. Adapted from F. Mastropietro et al., Nature Materials (2017).

[1] F. Mastropietro, P. Godard, M. Burghammer, C. Chevallard, J. Daillant, J. Duboisset, M. Allain, P. Guenoun, J. Nouet, V. Chamard, Revealing crystalline domains in a mollusc shell “single-crystalline” prism, Nature Materials (à paraître).
[2] P. Godard et al., Nature Communications 2, 568 (2011).
[3] S. O. Hruszkewycz, et al., Nature Materials 16, 244 (2017).

Link to other CNRS articles:>]

Institut Fresnel (CNRS Marseille), NIMBE (CEA-CNRS Gif-Sur-Yvette), GEOPS (Université Paris Saclay), Synchrotron Soleil (Gif-Sur-Yvette), ESRF (Grenoble).

Virginie Chamard, Equipe Comix (Institut Fresnel)
Tel 04 91 28 28 37 –

Corinne Chevallard, NIMBE (CEA-CNRS)
Tel 01 69 08 52 23 –

A new plasma assisted electron beam deposition machine in Espace Photonique

Within the framework of a project financed by the city of Marseille, the Thin Film Research team of Institut Fresnel has just installed a new Plasma assisted electron beam deposition machine (Bühler SYRUSpro 710) within the Espace Photonique. This AMU technological platform is already equipped with several state-of-the-art machines (e.g. Bühler HELIOS and Bühler SYRUSpro 710) and this new acquisition will help for the development of new and innovative thin film-based components. This machine will be dedicated to the deposition thin films made of infrared materials and to the development of thin layers made of unconventional materials such as phase changing materials (e.g. chalcogenides). In particular, it will enable us to develop broadband antireflection coatings [1.5-15] μm (R&T CNES project), volume structured components (DGA thesis) or optical metasurfaces (Multiwave-funded CIFRE thesis).

Contact RCMO Team: Julien Lumeau
Contact Marseille CityHall: Christophe VOLPE, Office "Immobilier d’Entreprises et Enseignement Supérieur Recherche, Ville de Marseille" -

Researchers of the MOSAIC team at Institut Fresnel have demonstrated the possibility to image, at sub-second time scales, the orientational dynamics of lipids in artificial and cell membranes, without the use of any fluorescence labels.
The gain in imaging rate with respect to other techniques is of a few orders of magnitude ; those methods required indeed minutes to form an orientational image of a few hundreds of micrometers in size.

Imagerie de l’orientation des lipides dans des couches lipidiques artificielles
S. Brasselet

The optical microscopy method used in the present work records nonlinear coherent Raman scattering signals, in the form of stimulated Raman scattering (SRS) or coherent anti-Stokes Raman scattering (CARS). Those signals originate from the resonant interaction of two pulsed beams with molecular vibrations, here targetting the CH bonds of membrane lipids. Matthias Hofer, Naveen Kumar Balla and Sophie Brasselet have used the lock-in detection method usually implemented for detecting modulated signals in SRS, which exploits modulation transfer from one of the applied incident beam to the other. Here they provided an incident modulation, not anymore in intensity, but rather in polarization. Polarized signals are sensitive to molecular orientations, therefore the obtained modulation is now the signature of molecules being aligned. This scheme has permitted to determine, for each pixel of the image at a rate of 50 microsecond per pixel, both angular distribution width and mean orientation, which are characteristics of molecular organization in the measured lipid membranes at the sub-micrometric scale.

Those signals are rich in information for fundamental and applied biomedical purposes, in particular in tissues such as myelin, a multilayer lipid structure which surrounds and protects our axons. This layered structure is highly perturbed when neurodegenerative diseases develop, such as in Alzheimer’s or multiple sclerosis. This technique could provide early detection of myelin membranes loss of adhesion and detachment, well before they can be visualized at a macroscopic scale. A demonstration of feasability has been recently performed in myelin in the mouse spinal cord, in a work submitted in collaboration with Franck Dbarbieux, INT Marseille.

Reference: M. Hofer, N.K. Balla, S. Brasselet, High speed polarization resolved Coherent Raman Scattering imaging, Optica Vol. 4, Issue 7, pp. 795-801 (2017)

See also: P. Gasecka, A. Jaouen, F.-Z. Bioud, H. Barbosa de Aguiar, J. Duboisset, P. Ferrand, H. Rigneault, N. Balla, F. Debarbieux, S. Brasselet, Degradation of molecular organization of myelin lipids in autoimmune demyelination probed by polarization resolved nonlinear vibrational microscopy, BioRxiV :

Contact: Sophie Brasselet- MOSAIC,

Deux lauréats ERC Consolidator pour l’Institut Fresnel

L’appel ERC Consolidator Grants du Conseil européen de la recherche récompense des chercheurs d’excellence ayant entre sept à douze ans d’expérience après leur thèse. Deux chercheurs de l’Institut Fresnel viennent d’obtenir ce financement s’élevant à environ 2 millions d’euros pour une période de cinq ans.

Virginie Chamard est responsable de l’équipe COMiX. Son projet « 3D-BioMat : Deciphering biomineralization mechanisms through 3D explorations of mesoscale crystalline structure in calcareous biomaterials » propose d’avancer dans la compréhension des processus de biominéralisation grâce au développement d’une nouvelle microscopie aux rayons X, en collaboration avec l’Ifremer (Polynésie Française) et le NIMBE (CNRS/CEA, Saclay).

Site web de l’équipe : COMIX

Jérôme Wenger travaille dans l’équipe MOSAIC. Son projet intitulé « TryptoBoost : Boosting tryptophan fluorescence with optical nanoantennas to watch label-free protein dynamics with single molecule resolution at high concentration » vise à étudier les dynamiques des interactions chimiques de protéines avec de nouveaux outils de microscopie et spectroscopie optiques.

Site web du chercheur :

Crystalline materials: imaging rapidly and efficiently

A new x-ray microscopy, three-dimensional, quantitative and highly-resolved, x-ray microscopy to explore crystalline nanostructures

Understanding shell growth, controlling the optical properties of semiconductors, or even improving the electrical performance of metallic materials are among the many scientific challenges that require knowing the fine properties of crystals at local scales. Due to their long penetration depth, X-rays allows us to probe the inside of a crystal. But producing a quantitative 3D image - providing crystalline strain field information, for instance - with nano-scale resolution remains extremely difficult as a result of the poor efficiency of the available lenses at these wavelengths.
The new approach developed by a Franco-American team and published in Nature Materials greatly simplifies and speeds up the process.

Over the last several years, a so-called lens-less microscopy has emerged: an image of the crystalline properties is retrieved from the diffracted intensities, and numerical methods are used in place of the lenses. To perform such an experiment, the x-ray beam must be coherent, as in the light delivered by a laser. However, the coherence at even the world’s brightest synchrotron x-ray sources is imperfect, such that the size of the sample that can be imaged with lens-less microscopy is typically of the order of a few microns. This hurdle has been cleared in 2011 by the team of V. Chamard at Institut Fresnel (Marseille, France) by demonstrating the possibility to extend arbitrarily the field of view without degrading the resolution.

This microscopy called Bragg ptychography leverages the spatial dependence of the diffraction patterns measured when a nano-focused x-ray beam is scanned along the sample surface. For each position, the 2D
diffraction pattern is recorded. The scanning step, much smaller than the size of the beam spot, produces a strong redundancy in the collected information that enables robust image reconstructions of the sample with new inversion algorithms. Furthermore, three-dimensional information is gained through a tomographic acquisition of the diffracted intensities. Typically, one must measure several hundreds diffraction measurements finely spaced in angle for each beam position on the sample. However, this approach leads to prohibitive total acquisition times (a few tens of hours),

and imposes strong measurement constraints that require specialized experimental set-ups (which only a few beamlines are able to provide), thus preventing the widespread adoption of Bragg ptychography in the scientific community.

The new approach, proposed jointly by researchers from Institut Fresnel (France) and the Argonne National Laboratory (US) greatly simplifies and speeds up this process. Indeed, a huge quantity of information is encoded by the scanning of the beam along the sample, so much so that it becomes possible to perform the measurement at a single viewing angle provided that the intersection between incident diffracted beams is spatially sufficiently well defined. This is indeed the case in Bragg ptychography. The introduction of a modified inversion algorithm gives access to this 3D information in a new and unique way – two dimensions arise from the diffracted signal and one dimension results from the spatial scanning. The new approach, called back-projection Bragg ptychography, marks a conceptual turning point in x-ray microscopy devoted to crystalline materials. The reduction of the total acquisition time, of about a factor 100, and the simplification of the geometry will enable explorations of complex crystalline materials that were not possible to date over a wide range of research areas such as life science and microelectronics.

References :
S. O. Hruszkewycz, M. Allain, M. V. Holt, C. E. Murray, J. R. Holt, P. H. Fuoss and V. Chamard, High-resolution three-dimensional structural microscopy by single-angle Bragg ptychography, Nature Materials 15, December 2016

Contact :
 Virginie Chamard, Institut Fresnel, Equipe Comix

 S. O. Hruszkewycz, Argonne National Laboratory, USA

Other CNRS Links :

 Actualités Scientifiques de l’INSIS, December 20, 2016 -
 "Relations internationales et Europe - ERC", Les Lauréats INSIS 2016 - Consolidator Grants, Virginie Chamard

A new route for looking deeper and brighter in biological tissues

Biological tissues are strongly scattering media, and as such, imaging with high resolution is still remarkably shallow. In particular, multiphoton imaging is strongly based on ballistic light (non-scattered, direction preserved). Because ballistic light intensity decreases exponentially in scattering media, it poses considerable challenges for imaging. Nevertheless, researchers recently found new ways to perform ultradeep imaging, with sub-cellular resolution, by recylcling scattered light itself. Building on these previous work, however exploiting an alternative strategy, we demonstrate record 4000-fold enhancement of nonlinear signal after scattering media, thus enabling highly contrasted nonlinear imaging of biological tissues (collagen fibers).

These remarkable results are possible because of the complex interference pattern arising from multiple scattering phenomena: the speckle. One can “reverse” the complex interference of the speckle into a deterministic shape, e.g. a bright focus. This focus is achieved by using various algorithms which are aided by a feedback mechanism. Traditionally, the feedback for nonlinear imaging is the nonlinear signal itself, which is dim and thus slow. In the new strategy proposed, we exploit the overwhelming linearly scattered light, in opposition to the traditional approach, as a feedback to achieve faster focusing capabilities.

Article :

Reference :
"Enhanced nonlinear imaging through scattering media using transmission-matrix-based wave-front shaping"

Hilton B. de Aguiar1,*, Sylvain Gigan2, and Sophie Brasselet1,†
Phys. Rev. A 94, 043830 – Published 18 October 2016

1Aix-Marseille Université, CNRS, Centrale Marseille, Institut Fresnel UMR 7249, 13013 Marseille, France
2Laboratoire Kastler Brossel, ENS-PSL Research University, CNRS, UPMC Sorbonne Universités, Collège de France, 24 rue Lhomond, 75005 Paris, France

Contact : -

Controlling light scattering and emission with silicon nanoparticles

Light can resonantly interact with subwavelength sized particles, leading to strong enhancements of light scattering and near field intensities in the surrounding of the particles. Metallic nanoparticles have attracted huge efforts over the last 20 years because they host localized surface plasmon resonances, electromagnetic resonances due to the collective oscillation of free electrons. But particles made of insulators can also host electromagnetic resonances, called morphologic or Mie resonances. Theoretical investications carried out at the Institut Fresnel demonstrated that morphologic resonances can yield to the same field enhancements than those yielded by plasmonics particles [1].

A research consortium which includes 2 laboratories of Marseille (Institut Fresnel & CINAM) has recently used the morphologic resonances in dielectric particles made of silicon to enhance to detect individual fluorescent molecules and to imprint colored images without pigments on a surface. Individual fluorescent molecules were observed in a 20 nm nanogap separating 2 silicon particles where the light intensity is strongly enhanced. Dielectric antennas were designed at the Institut Fresnel before being fabricated by the technological platforms hosted by the Institut Fresnel (Photonic space) and by CINAM (Planète) for the coating of the silicon layer and for the lithography and etching of the silicon antennas respectively. The coupling between the 2 silicon particles permits to create a detection volume of the fluorescent signal about one hundred zeptolitres (1 zL=10-21 L) (see the figure on the left). The average number of probed molecules in this volume is decreased by 3600× and becomes smaller than unity while the fluorescent signal is increased by more than 200× [2]. The morphologic resonances in silicon particles have also been used to imprint coloured images without pigment. The resonance frequency depending on the size of the shape of the particle, a palette of structural colours was created simply by moddifying the diameter of the particles. The interest of this technique was highlighted by reproducing a Mondrian’s painting at a 1:1200 scale thanks to silicon particles etched on a glass substrate (see the figure on the right) [3].

These recent advances have been performed without exciting surface plasmon resonances, and by using dielectric materials only. Silicon is ubiquitous in microelectronics and these results in nanophotonics pave the way to bridge the gap between resonant nanophotonics and opto-electronic devices based on silicon technology.

Figure : Gauche : Plateforme de détection moléculaire constituée de 2 particules de Si séparées par un interstice de 20 nm permettant d’exalter et de détecter le signal de fluorescence de molécules individuelles. Droite : Toile de Mondrian reproduite à l’aide de particules de Si. La coloration de ces particules résulte de l’interaction résonante avec la lumière. La couleur est contrôlée par la morphologie des particules
Références :
[1] « Plasmonics » with dielectrics, Optics & Photonics News, February 2016.
[2] Nano Lett. 16, 5143–5151 (2016). Doi : 10.1021/acs.nanolett.6b02076
[3] ACS Nano 10, 7761–7767 (2016). Doi : 10.1021/acsnano.6b03207

Contact Chercheur :
Nicolas BONOD – Institut Fresnel – Tel 04 91 28 28 35

Gold nanoparticles to maintain liquid water at 200°C at ambient pressure
Hydrothermal synthesis at ambient pressure using gold nanoparticles as nanosources of heat

Image de synthèse représentant des microcristaux obtenus par voie hydrothermale sur un tapis de nanoparticules d’or agissant comme nanosources de chaleur sous illumination laser.
Image de synthèse représentant des microcristaux obtenus par voie hydrothermale
sur un tapis de nanoparticules d’or agissant comme nanosources de chaleur sous illumination laser.
G. Baffou, Institut Fresnel

Artistic view of microcrystals obtained by hydrothermal synthesis using a layer of gold nanoparticles acting as nanosources of heat under laser illumination. In chemical synthesis, hydrothermal reactions involve liquid water between 100°C and 200°C as a solvent. In order to maintain a liquid state at such high temperatures, one has to use a pressure chamber, named an autoclave. This very common approach in chemistry suffers from many limitations, in particular because the reaction medium is closed.

Our researchers have demonstrated the possibility to conduct hydrothermal chemical reactions in an open medium, at ambient pressure, without boiling until 200°C. Such experimental conditions have been obtained at the microscopic scale using gold nanoparticles deposited on a glass substrate and locally heated using an optical microscope and a laser illumination. The absence of boiling up to 230°C and the persistence of a metastable state of water come from the natural absence of nucleation centres in the samples (such as microscopic scratches, dust and roughness).

The chemical reaction consists of the formation of microscopic crystals of indium hydroxide from a solution of indium chloride at 200°C in an aqueous solution, a textbook case in hydrothermal synthesis. Apart from the absence of boiling even at 200°C, other singular observations and interesting benefits have been evidenced, such as kinetics that are 1000 to 10000 times faster than in autoclaves.

This new chemical synthesis technique offers several advantages. As the medium is open, it is possible to add reactants during the reaction. Formation of products can also be observed using optical microscopy means. Finally, this techniques makes it possible as well to spatially structure the growth of solid products on a substrate using a laser beam, opening the path for new applications in micro and nanofabrication.

The concept was imagined by Guillaume Baffou, CNRS research scientist, and the experiments have been conducted by Hadrien Robert, Ph.D. student.
The gold nanoparticle samples have been fabricated by the teams of Julien Polleux (Max Plack Institute, Martinsried, Germany) and Romain Quidant (ICFO, Barcelona, Spain).

Références :
Light-Assisted Solvothermal Chemistry Using Plasmonic Nanoparticles
H. M. L. Robert, F. Kundrat, E. Bermúdez-Ureña, H. Rigneault, S. Monneret, R. Quidant, J. Polleux, and G. Baffou

ACS Omega

ACS Omega 1, 2 (juillet 2016)
DOI: 10.1021/acsomega.6b00019

Contact : Guillaume BAFFOU, CNRS research scientist MOSAIC group, Médaille de bronze 2015 du CNRS

Far-field diffraction microscopy at λ/10 resolution

Researchers of Institut Fresnel in Marseille and LPN Marcoussis

Published in OPTICA Vol 3, N°6, June 2016
Ting Zhang, Charankumar Godavarthi, Patrick Chaumet, Guillaume Maire, Hugues Giovannini, Anne Talneau, Marc Allain, Kamal Belkebir and Anne Sentenac
"Far-field diffraction microscopy at λ/10 resolution"

Tomographic diffraction microscopy is a three-dimensional quantitative optical imaging technique in which the sample is numerically reconstructed from tens of holograms recorded under different angles of incidence. We show that combining the measurement of the amplitude, the phase, and the polarization of the field scattered by the sample with an approximate knowledge of the sample permittivity allows reconstruction of spatially complex samples up to 50 nm resolution. This technique should be particularly useful for imaging objects made of known materials.

Optica - June 2016

Contact : Anne Sentenac, Researcher CNRS, SEMO Group - Phone : +334 91 28 27 90

Identify the good vibrations of molecules

Researchers at the Institut Fresnel in Marseille have developed an imaging technique to determine directly the organization of molecules in the material, and so reveal its structure at the molecular level. The measured signal is not only sensitive to the presence of the molecule but also specific in the way it vibrates, providing structural information previously untapped.

In an article published on 18 May 2016 in the journal Nature Communications, they describe how to shape the polarization of electromagnetic fields to specifically stimulate certain molecular vibrational modes. This method is based on the nonlinear coherent Raman process CARS (coherent anti-Stokes Raman scattering) and group theory concepts. Very simple to implement, this advanced technique is another step in label free microscopy. It offers new perspectives in biology and for biomedical diagnostics, areas where the optical microscope is an essential instrument.

Figure : Imaging of carbon-carbon bonds of myelin in a side section of spinal cord.
The circular structures correspond to the myelin sheaths surrounding the dendrites. The brightness of the image corresponds to the density of carbon-carbon bonds, the color scale corresponds to the organization of the bonds: the isotropic vibration are in red, the uni-directional vibration are in blue.
This image is obtained in a single acquisition without fluorescent probes, and thus allows to provide structural information on the organization of molecules in the sample (image 30 × 30 microns).

Reference : Carsten Cleff, Alicja Gasecka, Patrick ferrand, Hervé Rigneault, Sophie Brasselet et Julien Duboisset
Direct imaging of molecular symmetry by coherent anti-Stokes Raman scattering
Nature Communications 7, Article number 11562 (18 mai 2016)

Contact : Julien Duboisset, Maître de Conférences, Aix-Marseille University, Phone : +334 91 28 80 49

Ultra-wide-range measurements of thin-film filter optical density over the visible and near-infrared spectrum

Reference : M. Lequime, S Liukaityte, M. Zerrad, C. Amra, “Ultra-wide-range measurements of thin-film filter optical density over the visible and near-infrared spectrum,” Opt. Express 23, 26863-26878 (2015).
Selected by Advanced in Enginnering as a Key Scientific Article

See also the paper on NKT Photonics website "EXTREME optical metrology: First broadband measurement of a 12 optical density with 1 nm resolution".

More details on INSIS website (CNRS)

Contact : Michel Lequime and Myriam Zerrad

"Three dimensional nanometer localization of nanoparticles to enhance super-resolution microscopy" Nature Communications du 27 juillet 2015