cryoSENSE: Compressive Sensing Enables High-throughput Microscopy with Sparse and Generative Priors on the Protein Cryo-EM Image Manifold

Cryo-electron microscopy (cryo-EM) enables the atomic-resolution visualization of biomolecules; however, modern direct detectors generate data volumes that far exceed the available storage and transfer bandwidth, thereby constraining practical throughput. We introduce cryoSENSE, the computational realization of a hardware-software co-designed framework for compressive cryo-EM sensing and acquisition. We show that cryo-EM images of proteins lie on low-dimensional manifolds that can be independently represented using sparse priors in predefined bases and generative priors captured by a denoising diffusion model. cryoSENSE leverages these low-dimensional manifolds to enable faithful image reconstruction from spatial and Fourier-domain undersampled measurements while preserving downstream structural resolution. In experiments, cryoSENSE increases acquisition throughput by up to 2.5$\times$ while retaining the original 3D resolution, offering controllable trade-offs between the number of masked measurements and the level of downsampling. Sparse priors favor faithful reconstruction from Fourier-domain measurements and moderate compression, whereas generative diffusion priors achieve accurate recovery from pixel-domain measurements and more severe undersampling. Project website: https://cryosense.github.io.

Segment Anything Model for Zero-shot Single Particle Tracking in Liquid Phase Transmission Electron Microscopy

Liquid phase transmission electron microscopy (LPTEM) offers an unparalleled combination of spatial and temporal resolution, making it a promising tool for single particle tracking at the nanoscale. However, the absence of a standardized framework for identifying and tracking nanoparticles in noisy LPTEM videos has impeded progress in the field to develop this technique as a single particle tracking tool. To address this, we leveraged Segment Anything Model 2 (SAM 2), released by Meta, which is a foundation model developed for segmenting videos and images. Here, we demonstrate that SAM 2 can successfully segment LPTEM videos in a zero-shot manner and without requiring fine-tuning. Building on this capability, we introduce SAM4EM, a comprehensive framework that integrates promptable video segmentation with particle tracking and statistical analysis, providing an end-to-end LPTEM analysis framework for single particle tracking. SAM4EM achieves nearly 50-fold higher accuracy in segmenting and analyzing LPTEM videos compared to state-of-the-art methods, paving the way for broader applications of LPTEM in nanoscale imaging.