Advancing In-Situ and ex-Situ Transmission Electron Microscopy with Low Dose Focal Series Reconstruction and 4D‑STEM

Recent advances in transmission electron microscopy (TEM) have pushed spatial resolution into the 0.5 Å regime, shifting imaging from an instrument-limited to an object-limited discipline and enabling the direct visualization of individual atoms and molecules. However, the structures and dynamics of many functional materials, particularly catalysts, are strongly influenced by their local environment, creating challenges for imaging under conventional high‑vacuum and high‑dose conditions. In this seminar, two complementary developments in instrumentation and imaging methodology will be presented, each expanding the capabilities of TEM for both in‑situ and ex‑situ studies. First, open‑cell TEM, also known as environmental TEM (ETEM), will be described. The VISION PRIME platform, built on an ultra-stable SPECTRA ETEM system, will be introduced. Through the integration of a 5th-order aberration corrector, monochromated illumination, differential pumping that enables operation at 10-20 mbar gas pressure, and direct electron detection, a 0.5 Å information limit is maintained even in gas atmospheres. Using Young’s fringes and exit wave phase reconstruction, atomic‑resolution visualization of gas–surface interactions on a Au nanoparticle at 1 mbar N₂ has been demonstrated, revealing gas-dependent variations in atomic column widths and enabling operando studies of catalytic processes. Second, examples of exit wave phase reconstruction obtained using a low dose focal series reconstruction (LD‑FSR) methodology will be presented. This approach enables 1.6 Å‑resolution imaging of organic materials with limited radiation damage to the sample. By rapidly recording hundreds of low dose frames at cryogenic temperatures and reconstructing the exit plane wavefunction, aberration-corrected phase images up to the microscope’s information limit are obtained. In this way, access is provided to organic crystal structures and aperiodic features that would otherwise be obscured under strong defocus conditions and low signal-to-noise ratio. When combined with complementary methods such as density functional theory, reliable determination of molecular packing and local structural distortions is enabled directly from real-space images. Finally, a combined approach employing LD-FSR and 4D-STEM for imaging sensitive organic crystalline polymers will be demonstrated.