EMCFsys: A scalable ecosystem for high-throughput nanoscale ultrastructure analysis across biological kingdoms

Volume electron microscopy (vEM) provides nanoscale 3D visualization of cellular ultrastructure, but large-volume imaging and analysis remain limited by long acquisition times and annotation-intensive processing. Here we present the Electron Microscopy Cell Foundation ecosystem (EMCFsys), comprising a curated dataset of 4,002,802 high-quality electron micrographs spanning 14 modalities and major biological kingdoms, a foundation image restoration model (EMCellFiner) that enables 16-fold faster acquisition through high-fidelity super-resolution from low-resolution or low-dwell-time scans, and a foundation model (EMCellFound) that supports zero- to few-shot organelle classification, 2D segmentation, and precise 3D reconstruction. This facilitates high-precision 3D ultrastructure reconstruction, even for multi-piece organelles like the endoplasmic reticulum by using as little as 0.01% labeled data. Integrated into a zero-code Napari plugin, the ecosystem enables automated, high-throughput nanoscale analysis without programming expertise. By substantially reducing imaging time, annotation burden, and computational barriers, EMCF establishes an efficient, generalizable platform for large-scale vEM studies across cell types and species.