Applications of Event-Based Direct Detectors in Cryo-Electron Microscopy

Abstract The Direct Electron Apollo camera represents a major advancement in cryo-electron microscopy (cryo-EM) through its event-based electron counting (EBEC) architecture, which detects individual electron events in real time. This design minimizes coincidence loss and improves detective quantum efficiency (DQE) and signal-to-noise ratio (SNR) across a wide range of dose rates. Apollo’s performance has been demonstrated across multiple cryo-EM applications. In single-particle analysis (SPA), it achieves sub-2 Å reconstructions at high dose rates, outperforming frame-based detectors limited by coincidence loss. In cryo-electron tomography (cryo-ET), its fast frame rate and low coincidence loss enables further development of advanced acquisition schemes such as fast incremental single exposure (FISE) and continuous-rotation tomography, improving throughput and image quality. For micro-electron diffraction (microED), Apollo captures atomic-resolution data in under a minute by accurately detecting both strong and weak diffraction signals, reaching resolutions as fine as 0.5 Å. Across all techniques, Apollo’s high DQE, rapid readout, and efficient on-chip processing offer improved resolution, faster acquisition, and greater experimental flexibility, setting a new standard for detector performance in structural biology.