Imagerie pour la biologie et la santé (IBS)

Imagerie optique plein champ d'un explant de rétine de souris

Responsable

Emmanuel FORT

Tél. : 01 80 96 30 35

Co-responsable

Ignacio IZEDDIN

Tél. : 01 80 96 30 75

Membres permanents

Michael ATLAN

Tél. : 01 80 96 30 36

Pedro BARAÇAL DE MECÊ

Tél. : 01 80 96 30 51

Claude BOCCARA

Tél. : 01 80 96 30 44

Maïmouna BOCOUM

Tél. : 01 80 96 30 76

Clément CABRIEL

Tél. : 01 80 96 30 59

Bruce DENBY

Emmanuel FORT

Tél. : 01 80 96 30 35

Ros-Kiri ING

Tél. : 01 80 96 30 41

Ignacio IZEDDIN

Tél. : 01 80 96 30 75

François RAMAZ

Tél. : 01 80 96 30 47

Olivier THOUVENIN

Tél. : 01 80 96 30 51

Actualités

Transmission interference microscopy of anterior human eye Alhaddad S., , Ghouali W., Baudouin C., A. C. Boccara, and V. Mazlin Nature Communications 16, no. 1 (2025) Résumé: Cellular imaging of the human anterior eye is critical for understanding complex ophthalmic diseases, yet current techniques are constrained by a limited field of view or insufficient contrast. Here, we demonstrate that Ernst Abbe’s foundational principles on the interference nature of transmission microscopy can be applied in vivo to the human eye to overcome these limitations. The transmission geometry in the eye is achieved by projecting illumination onto the posterior eye (sclera) and using the back-reflected light as a secondary illumination source for anterior eye structures. Specifically, we show that the tightly localized illumination spot at the sclera functions analogously to a closed condenser aperture in conventional microscopy, significantly enhancing interference contrast. This enables clear visualization of cells and nerves across all corneal layers within an extended 2 mm field of view. Notably, the crystalline lens epithelial cells, fibers, and sutures are also distinctly resolved. In patients, Fuch’s endothelial dystrophy - a major ophthalmic disease affecting 300 million people - is highlighted under a transmission contrast, providing complementary information to traditional reflection contrast. Constructed using consumer-grade cameras, the instrument offers a path toward broad adoption for pre-screening and surgical follow-up, as well as for diagnosing corneal infections in low-resource settings, where anterior eye diseases are most prevalent.
Quantitative evaluation of methods to analyze motion changes in single-particle experiments Muñoz-Gil, G., H. Bachimanchi, J. Pineda, B. Midtvedt, G. Fernández-Fernández, B. Requena, Y. Ahsini, S. Asghar, J. Bae, F. J. Barrantes, S. W. B. Bender, C. Cabriel, J. A. Conejero, M. Escoto, X. Feng, R. Haidari, N. S. Hatzakis, Z. Huang, I. Izeddin, H. Jeong, Y. Jiang, J. Kæstel-Hansen, J. Miné-Hattab, R. Ni, J. Park, X. Qu, L. A. Saavedra, H. Sha, N. Sokolovska, Y. Zhang, G. Volpe, M. Lewenstein, R. Metzler, D. Krapf, G. Volpe, and C. Manzo Nature Communications 16, no. 1 (2025) Résumé: The analysis of live-cell single-molecule imaging experiments can reveal valuable information about the heterogeneity of transport processes and interactions between cell components. These characteristics are seen as motion changes in the particle trajectories. Despite the existence of multiple approaches to carry out this type of analysis, no objective assessment of these methods has been performed so far. Here, we report the results of a competition to characterize and rank the performance of these methods when analyzing the dynamic behavior of single molecules. To run this competition, we implemented a software library that simulates realistic data corresponding to widespread diffusion and interaction models, both in the form of trajectories and videos obtained in typical experimental conditions. The competition constitutes the first assessment of these methods, providing insights into the current limitations of the field, fostering the development of new approaches, and guiding researchers to identify optimal tools for analyzing their experiments.
Label-free metabolic imaging and energy costs in Chlamydomonas Boccara, M., K. Wostrikoff, B. Bailleuil, and C. Boccara The European Physical Journal E 48, no. 6-7 (2025) Résumé: We developed a label-free optical microscopy method to study movements of different frequencies and amplitudes within a cell. We use optical transmission tomography (OTT) that operates in transmission, and we record the changes of signal values of all the pixels of movies taken for a few seconds (dynamic signal). This signal is a metabolic signal in algae as it decreased in the presence of photosystem II inhibitors or when samples were illuminated at wavelengths where the photoreceptors are poorly operative. We used as model organism Chlamydomonas for which mutants are available. We used a mutant deleted of the chloroplastic gene encoding the large subunit of the Rubisco, ΔrbcL. This mutant is unable to fix atmospheric CO<inf>2</inf> and is devoid of pyrenoid. We compared the dynamic signal between wild-type strain and ΔrbcL mutant of Chlamydomonas grown in dark condition and found it to be 5 to 10 times higher. This mutant overproduced starch, and we tempted to associate the metabolic signal to the cost in ATP<inf>eq</inf> consumption for building starch. The method is easy to implement and could be very valuable for studies of phytoplankton in situ or virus-infected cells.
Hybrid quantum network for sensing in the acoustic frequency range Novikov, V., J. Jia, T. B. Brasil, A. Grimaldi, M. Bocoum, M. Balabas, J. H. Müller, E. Zeuthen, and E. S. Polzik Nature 643, no. 8073, 955-960 (2025) Résumé: Ultimate limits for the sensing of fields and forces are set by the quantum noise of a sensor<sup>1, 2–3</sup>. Entanglement allows for suppression of such noise and for achieving sensitivity beyond standard quantum limits<sup>4, 5, 6–7</sup>. Applicability of quantum optical sensing is often restricted by fixed wavelengths of available photonic quantum sources. Another ubiquitous limitation is associated with challenges of achieving quantum-noise-limited sensitivity in the acoustic noise frequency range relevant for several applications. Here we demonstrate a tool for broadband quantum sensing by performing quantum state processing that can be applied to a wide range of the optical spectrum and by suppressing quantum noise over an octave in the acoustic frequency range. An atomic spin ensemble is strongly coupled to one of the frequency-tunable beams of an Einstein–Podolsky–Rosen (EPR) source of light. The other EPR beam of light, entangled with the first one, is tuned to a disparate wavelength. Engineering the spin ensemble to act as a negative-mass or positive-mass oscillator, we demonstrate frequency-dependent quantum noise reduction for measurements at the disparate wavelength. The tunability of the spin ensemble enables targeting quantum noise in a variety of systems with dynamics ranging from kHz to MHz. As an example of broadband quantum noise reduction in the acoustic frequency range, we analyse the applicability of our approach to gravitational-wave detectors (GWDs). Other possible applications include continuous-variable quantum repeaters and distributed quantum sensing.

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Présentation du thème

Le thème IBS étudie les processus et tissus biologiques de l’échelle nanoscopique à macroscopique. Via l’étude approfondie de l’interaction entre différentes ondes et la matière biologique, de nouvelles méthodes d’imagerie non conventionnelles sont développées. L’imagerie de super-résolution permettant de sonder l’organisation de la matière à l’échelle de la molécule individuelle et de comprendre le transport de ces molécules dans l’environnement de la cellule et en particulier dans le noyau. L’équipe imagerie optique plein champ s’intéresse à l’organisation des tissus biologiques par des techniques de microscopie interférométrique sans marquage, et permettant d’étudier la viabilité des cellules et tissus d’un organisme via le suivi des organelles cellulaires, pour des applications tant de biologie fondamentale que de diagnostic médical in vivo. L’équipe imagerie Doppler holographique de la rétine est spécialisée dans la quantification des flux sanguins dans la rétine de patients humains. Néanmoins, les approches optiques présentées jusqu’à là sont limitées à des faibles profondeurs de pénétration dans le corps humain (en dehors de l’œil transparent). Afin de pouvoir sonder les tissus biologiques plus en profondeur, il devient nécessaire d’utiliser d’autres types d’ondes, en particulier les ondes acoustiques. L’imagerie acousto-optique permet d’obtenir des images de tissus avec un contraste optique à plusieurs millimètres de profondeur en marquant les photons multiplement diffusés grâce aux ondes acoustiques. Finalement, l’utilisation d’ondes acoustiques permet à l’équipe Mouvements de surface de cartographier les déformations vibratoires du thorax sans contact et de manière non invasive.

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