A fast detector for dose efficient scanning Transmission Electron Microscopy of thick sample biological and environmental systems

Studying environmental resources is critical for the Department of Energy’s Biological and Environmental Research division to achieve a predictive understanding of complex biological, earth, and environmental systems for energy and security. Molecular and subcellular-level characterization of plants and microbes can provide insight into energy solutions including biofuel production and improve the understanding of changes in the earth and environment due to climate change. While cryo electron microscopy is well-suited for studying isolated molecular structures, its application to environmental research, particularly for examining thick sections of cells or organo-mineral interfaces, presents significant challenges. The thicker sections required for these studies increase the likelihood of chromatic blur from inelastic scattering, a phenomenon that arises from the varying speeds of electrons of different energies, leading to reduced contrast in the tomographic images. Scanning transmission electron microscopy is far less sensitive to inelastic scattering blur, but traditional scanning transmission electron microscopy imaging remains inefficient due to the limited number of scattered electrons used to form the signal. Recent advancements in detector technology have led to highly efficient imaging modes, such as Tilt-Corrected Bright Field Imaging, which has demonstrated a threefold improvement in information limit over conventional transmission electron microscopy in thick cellular samples at the same dose. As tilt-corrected bright field images share the same contrast mechanisms as transmission images used in cryo-electron microscopy, integrating this technique into existing cryo-electron microscopy workflows should be easier than implementing other methods. The primary challenge is developing detectors that can rapidly capture data fast enough to maintain image resolution while accommodating the thick sample imaging and tomography techniques. This Phase I project will be a collaborative endeavor to design a scalable, high-speed detector capable of addressing the evolving needs of the electron microscopy community. The initial objective will be to comprehensively evaluate emerging detector technologies against the stringent requirements of electron microscopy, encompassing read-out electronics and sensor technologies. Subsequently, a system design will be developed to serve as a foundation for prototype fabrication during the Phase II effort. The sensor component will be optimized for 300 keV operation and integrate with existing electron microscope architectures. Following the establishment of top-level specifications, preliminary system designs will be generated, including a carrier board tailored to the selected sensor and read-out electronics. This technology will enable more dose-efficient imaging of proteins and cells, empowering researchers within Biological and Environmental Research divisions to delve deeper into the intricate mechanisms of cellular trans-membrane transport and microbial interactions within soils. Moreover, this technology will facilitate investigations focused on the interactions between viruses and host cells, potentially leading to the development of novel therapy treatments.