Liquid-phase 3D electron microscopy for materials science and biology

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Electron microscopy has traditionally been associated with the study of thin, solid samples in vacuum. In the last decade, a few groups pioneered systems achieving nanometer resolution for liquid specimens. The broad applicability of liquid phase electron microscopy (LPEM) has driven a wave of interest as it has opened exciting possibilities for solving grand challenges in materials science, chemistry, biology, and other fields, and has opened the route for operando studies. Whatever the application field, a three-dimensional (3D) representation of the sample in liquid is often required for understanding its structure. The primary method currently used for obtaining insight into the 3D structure at the nanometer scale of unique samples from biology and materials science is tilt-series transmission electron microscopy. In particular, scanning transmission electron microscopy (STEM) is well-adapted to the study of thick specimens such as liquid samples. The goal of this proposal is to establish Liquid 3D STEM as new microscopy modality, presenting an unique way for nanoscale characterization of samples in liquid from both materials science and biology. Liquid 3D STEM has enhanced capabilities compared to state-of-the-art 3D electron microscopy because it provides a means to study specimens in liquid. The project benefits from the synergy of two leading centers for in situ electron microscopy, INSA in Lyon, with a focus on materials science, and INM in Saarbrücken (Germany), with research focused towards biophysics. The technique will be jointly developed by gathering the complementary expertise of both groups. Each group will use Liquid 3D STEM to study a system with which it has already several years of experience. By combining efforts and expertise, we expect to be able to overcome the main difficulties encountered during the experiments (sensitivity to the electron beam, low contrast, large thickness). Establishing this technique would open up a novel way for nanoscale characterization of samples from materials science and biology. The project consists of 4 work packages (WPs). Two of them are dedicated to instrumentation: theoretical and computational aspects (WP1), and implementation of Liquid 3D STEM with optimized microscope settings (WP2). The two other WPs involve the application of the newly-established technique to materials science (determination of the surfactant distribution in latex suspensions, WP3), and to biological samples (study of nanoparticle intercellular fate, WP4).