ultra-High-spEed high-Resolution force Microscopy and spEctroscopy of biological Systems – HERMES

The 4 scientific tasks of the HERMES project are as follows: (i) Design and operation of ultra-fast optomechanical AFM probes in liquid media, up to GHz (ii) Fabrication of silicon optomechanical probes, (iii) Instrumentation and system integration for very high speed force spectroscopy and imaging, (iv) AFM spectroscopy and microscopy experiments on biomolecular systems. To accomplish these, HERMES relies on a consortium of 4 laboratories: LAAS-CNRS in Toulouse, CEA-LETI in Grenoble, MPQ-Univ. Paris-CNRS in Paris and DyNaMo in Marseille. Part of this consortium has already worked together during the OLYMPIA project. In the framework of HERMES, it integrates a biophysics team to accomplish achievements of biological utility. Each team is an expert in its field (AFM instrumentation at LAAS, silicon photonics and MEMS technologies at CEA-LETI, optomechanics -including in liquids- at MPQ, high speed AFM for biology at DyNaMo).

Significant advances have been achieved on several key aspects of the project:

Design and fabrication of optomechanical components: We have conducted an in-depth study of optical and mechanical modes to design probes capable of operating up to 1 GHz. Collective fabrication of these devices has been carried out using «silicon photonics« technology. These components have been characterized, validating the theoretical design.

Probe releasing technologies: We have developed two complementary methods to create protruding tips, a crucial element for AFM applications: (i) a semi-collective method combining saw dicing and plasma etching, and (ii) a fully collective method at the wafer scale, using precisely controlled alignment and backside etching techniques.

Actuation in liquid environment: We have studied and experimentally implemented different approaches for actuating optomechanical probes in liquid medium, exploring both optical and electrical methods to determine the optimal solution.

Biophysical applications: Preliminary measurements in AFM force spectroscopy have been performed to study the unfolding of bacteriorhodopsin (experiments in air), demonstrating the ability to address relevant biological questions.

Thanks to its interdisciplinary nature, the project will naturally benefit from a wide visibility in the AFM, optomechanical systems and biomolecular physics communities. At the end of the project, the very high-speed probes and instruments developed in HERMES will provide access to the fast dynamics of biological nanosystems, down to the nanosecond. Expectations are particularly high in the field of nano-scale biology, where the major challenge of understanding the relationship between conformational changes in molecules and their biological functions is a major experimental challenge in native physiological environments.

Suyambulingham Subramanian, Nicolas Mauran, Chérif Bélacel, Guillaume Jourdan, Ivan Favero, et al.. Unveiling Hidden Dynamics of Biological Process with Optomechanical AFM with sub-µs time resolution. Annual Meeting of the GDR MecaQ, Sep 2024, Grenoble, France. ?hal-04819714?

Aleksandra Markovic, Mathis Lefebvre, Laurent Mazenq, Samuel Charlot, Marc Gély, et al.. Suspended tip overhanging from chip edge for atomic force microscopy with an optomechanical resonator. Journal of Optical Microsystems, 2024, 4 (3), pp.033501. ?10.1117/1.JOM.4.3.033501?. ?hal-04689661?

Suyambulingham Subramanian, Clément Le Fur, Lucien Schwab, Ilan Shlesinger, Pierre Allain, et al.. Sondes optomécaniques : vers l'AFM aux fréquences GHz. Forum de microscopie à sondes locales, Apr 2024, Lyon, France. ?hal-04562805?

Kateryna Muzyka, Felix Rico, Guobao Xu, Ignacio Casuso. DNA at conductive interfaces: What can atomic force microscopy offer?. Journal of Electroanalytical Chemistry, 2023, 938, pp.117448. ?10.1016/j.jelechem.2023.117448?. ?hal-04476926?

Brevet français n° priorité FR2212956 déposé le 08/12/2022
Extension internationale déposée le 29/11/2023, PCT/EP2023083447
Demandes publiées : FR3143140 (A1) 2024-06-14 et WO2024120911 (A1) 2024-06-13
Dispositif à résonateur optique, mécanique ou opto-mécanique
G. Jourdan, M. Gély, I. Favero, B. Legrand

HERMES wants to take high-speed atomic force spectroscopy and microscopy (AFM) to the next level, opening a new experimental window in molecular biophysics experiments. We will develop nanosecond atomic force tracking in liquids and ultra-high-speed force imaging, with a spatial and force resolution at the level of molecular chemical bonds. These breakthroughs are made possible by a new paradigm of optomechanical AFM probes that have recently been demonstrated at intermediate frequencies in air and vacuum by the partners, placing them at the forefront of the developments. The mechanical resonance frequency f of the probe governs both the measurement bandwidth and the force resolution. This frequency can be considerably increased by using optomechanical transduction. Thanks to a convergence between silicon photonics, optomechanics and large-scale integrated MEMS/NEMS technologies, the HERMES probes will operate in liquid media and their frequency will rise up to GHz. In addition, developments will be carried out in electronics, probe positioning, data acquisition and processing, in order to fully exploit this very high frequency in an AFM microscope. In parallel, biophysical experiments will be carried out with these optomechanical probes, making it possible to reach, at short times, regimes and phenomena hitherto unexplored in molecular complexes, such as molecular folding. These experiments will in turn feed technological and instrumental developments, but will also help to answer open questions on the rapid dynamics of biomolecules, by broadening the time scales on which force data can be compared with molecular dynamics simulations (usually performed between ps and ms). The 4 scientific tasks of the HERMES project are as follows: (i) Design and operation of ultra-fast optomechanical AFM probes in liquid media, up to GHz (ii) Fabrication of silicon optomechanical probes, (iii) Instrumentation and system integration for very high speed force spectroscopy and imaging, (iv) AFM spectroscopy and microscopy experiments on biomolecular systems. To accomplish these, HERMES relies on a consortium of 4 laboratories: LAAS-CNRS in Toulouse, CEA-LETI in Grenoble, MPQ-Univ. Paris-CNRS in Paris and LAI-INSERM in Marseille. Part of this consortium has already worked together during the OLYMPIA project. In the framework of HERMES, it integrates a biophysics team to accomplish achievements of biological interest. Each team is an expert in its field (AFM instrumentation at LAAS, silicon photonics and MEMS technologies at CEA-LETI, optomechanics -including in liquids- at MPQ, high speed AFM for biology at LAI). Thanks to its interdisciplinary nature, the project will naturally benefit from a wide visibility in the AFM, optomechanical systems and biomolecular physics communities. At the end of the project, the very high-speed probes and instruments developed in HERMES will provide access to the fast dynamics of biological nanosystems, down to the nanosecond. Expectations are particularly high in the field of nano-scale biology, where the major challenge of understanding the relationship between conformational changes in molecules and their biological functions is a major experimental challenge in native physiological environments.