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New Krios 5 Cryo-TEM from Thermo Fisher delivers up to 25% throughput gain for atomic-resolution analysis

By Brian Buntz | April 8, 2025

[Image courtesy of Thermo Fisher Scientific]

Thermo Fisher Scientific has introduced its next-generation Krios 5 Cryo-Transmission Electron Microscope (Cryo-TEM). The firm boasts that the microscope delivers up to a 25% increase in throughput for atomic-resolution analysis compared to previous models. This performance leap stems from enhanced optical precision combined with new AI-assisted automation features, including the the company’s Smart EPU Software, which is designed to simplify complex setups and improve overall data fidelity for techniques like single particle analysis (SPA) and cryo-electron tomography (cryo-ET).

These combined features are designed to support structural and cellular biology research relevant to drug discovery and the development of new therapies. The Krios 5 facilitates higher fidelity 3D visualization of proteins and molecular machines, showing their localization and dynamics within the cell architecture, enabling more detailed study of biological mechanisms at the atomic level. For cryo-ET applications, the system includes a new vacuum capsule transfer mechanism engineered to reduce sample contamination and help maintain structural integrity during loading.

Operating at 300 kV, the Krios 5 uses an optical platform engineered for stability and high performance. High resolution and contrast are supported by key optional components like the low-energy-spread cold field emission gun (E-CFEG) delivering <0.3 eV energy spread, the Selectris X Imaging Filter for stable zero-loss energy filtering, and the Falcon 4i Direct Electron Detector. This detector features high Detective Quantum Efficiency (DQE) and supports Electron Event Representation (EER) decoding for flexible data handling. Performance specifications contributing to throughput and data consistency include magnification calibration accuracy better than 1% and an extended Aberration-Free Image Shift (AFIS) range of up to 20 µm, which minimizes mechanical stage movements during large area data acquisition.

The system uses advanced automation and integrated software to drive efficiency in other ways. For instance, for single particle analysis (SPA), the Smart EPU Software incorporates AI-based plugins to assist with automated grid screening, parameter adjustments, and real-time quality monitoring. For cryo-electron tomography (cryo-ET), the CryoTomo Software Suite enables unattended multi-grid acquisitions. It features on-the-fly motion correction and reconstruction capabilities. For the cryo-ET workflow, the optional Vacuum Capsule provides contamination-reduced transfer of focused ion beam (FIB) milled cryo-lamellae, aiming to preserve sample integrity between instruments.

An illustration of the Phycobilisome protein complex (PDB 7SC8) — harvesting light in blue-green algae in a a Thermo Fisher brochure

An illustration of the Phycobilisome protein complex (PDB 7SC8) — harvesting light in blue-green algae in a Thermo Fisher brochure

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