How the SXT-100 Empowers Core Imaging Labs

Core Imaging Lab Managers face mounting pressure to deliver faster, higher-quality cryo-imaging results to their internal customers while adapting to a rapidly evolving set of scientific demands. As structural biology moves beyond isolated molecules toward “imaging across scales” – from tissue and organoid models down to molecular detail – facilities must now handle more diverse sample types, more complex correlative workflows, and tighter timelines. These advances bring new challenges in sample handling, preparation, and environmental control, alongside the existing demands of maximising throughput, maintaining instrument uptime, and supporting an expanding user base.

Meeting these expectations requires not just incremental improvements to current workflows, but the strategic adoption of complementary technologies that address both today’s operational bottlenecks and tomorrow’s research needs.

The SiriusXT SXT-100, a lab-scale cryo-soft X-ray microscope, directly addresses these challenges by offering high-resolution, native-contrast, 3D imaging of fully hydrated, intact cells and small tissue sections – without sectioning or labelling – and without damaging the sample.

In addition to increasing imaging throughput, cryo-soft X-ray tomography (cryo-SXT) delivers more sample-volume context than electron tomography, improving the interpretation of EM data from thinned samples. And because it is non-destructive, it integrates naturally into workflows that image across scales, from tissue to molecular characterisation, even in workflows where labelling between biopsy and freezing is not possible.

The Current Landscape: Core Lab Challenges in Cryo-Imaging

Throughput and Scheduling Pressure

• Cryo-EM systems are in constant demand, with weeks-long booking queues at many facilities.
• One whole-cell tomogram via cryo-ET may require days of sample preparation (FIB milling) and imaging.
• High-end instruments are often tied up on projects that could be triaged earlier in the workflow.

Impact: Delays frustrate users, slow research outputs, and limit the number of projects a core can support.

Sample Preparation Bottlenecks

• For cryo-ET, most biological specimens are too thick for direct EM imaging and must be thinned using a cryo-FIB or cryo-ultramicrotome.
• These processes are complex, have high failure rates, and are a major source of ice contamination (~36% of samples in some surveys).
• In tissue biopsies and organoid models, where staining between sampling and cryo-freezing is generally not possible, capturing structural context requires a label-free, native-contrast method.

Impact: Low yield reduces effective throughput, increases the cost per usable dataset, and limits structural interpretation in complex tissue.

Correlation Across Scales

• Cryo-fluorescence, where sample labelling has been possible, identifies regions of interest but is generally limited to ~300–500 nm resolution.
• Cryo-EM provides near-atomic resolution but on small, thin samples that are 100 nm to 150 nm thick.
• This leaves a “resolution gap” and a “volume gap” – larger-scale ultrastructure (between 100 nm and 300 nm in size) and surrounding context are invisible, making it harder to confidently target rare events or interpret molecular interactions in situ.

Impact: Poor targeting wastes valuable cryo-EM time and risks missing key biological insights, especially in complex multicellular environments.

The SXT-100: Closing the Gaps

The SXT-100 is the first commercial, lab-based cryo-soft X-ray microscope designed for biological research. It complements existing cryo-EM and fluorescence workflows by imaging whole, fully hydrated cells and small tissue sections at 40–50 nm resolution in 3D – without labelling, sectioning, or FIB milling – and without damaging the sample for downstream EM.

Increasing Throughput and Preserving EM Capacity

• Whole-cell volumes (up to 10 μm thick) can be imaged in 30–90 minutes, allowing rapid survey of multiple cells or regions.
• Enables triage: use SXT to identify target cells and events, then allocate cryo-EM time only to those that warrant atomic-resolution follow-up.
• Frees up high-end cryo-EM instruments for the work they are uniquely suited to.

Result: More projects completed, faster turnaround, and higher-value use of existing cryo-EM assets.

Providing More Volume Context for EM Data

• SXT’s non-destructive, whole-volume imaging reveals the structural surroundings of regions later imaged by electron tomography.
• In FIB-milled lamellae, cryo-EM captures a small, 150 nm thick slice of the cell – SXT shows how that slice fits into the whole-cell architecture, aiding interpretation of molecular structures in their true biological setting.
• In tissue samples, SXT captures multicellular arrangements, vasculature, and extracellular matrix in 3D without any chemical stains or labels – essential when samples must go directly from biopsy to freezing.

Result: Richer datasets, better-informed EM analysis, and the ability to interpret molecular detail in its native spatial context.

Streamlining Sample Transfer and Reducing Contamination Risk

• The SXT-100 is compatible with the same cryo-sample holders used in leading cryo-EM instruments, allowing grids to be transferred directly between systems without remounting.
• A common carrier format means fewer handling steps, reducing opportunities for environmental exposure and greatly lowering the risk of ice contamination – a significant cause of sample loss in cryo workflows.
• The ability to move the exact same vitrified sample between SXT and EM enables true same-sample correlation, improving reliability and confidence in the results.

Result: Higher sample survival rates, better correlation accuracy, and more efficient use of precious specimens.

Bridging the Resolution and Scale Gaps in Correlative Workflows

• Delivers 3D images with enough resolution to resolve organelles, large protein complexes, and pathogens in situ.
• Bridges the jump from ~300 nm cryo-fluorescence to sub-nm cryo-EM, enabling precise targeting of rare or subtle events.

Result: Enables confident targeting of downstream cryo-EM, maximising the value of every sample and imaging run.

Optimising Staff and IT Resources

• The SXT-100 is designed with usability in mind. Its interface supports rapid adoption by facility staff, reducing the training burden and dependence on niche operator expertise.
• Automation-readiness and intuitive workflows free up skilled personnel to focus on high-value tasks while still delivering consistent, high-quality imaging.
• SXT datasets are relatively lightweight compared to cryo-EM, reducing the storage and processing burden on IT systems and enabling smoother integration into standard facility infrastructure.

Result: Lower operational complexity, faster onboarding, and reduced IT strain – all contributing to a more scalable imaging capability.

Strategic Benefits for Core Lab Managers

• Diversifies Service Portfolio: Attracts users from cell biology, pathology, and drug discovery who need mesoscale, whole-volume imaging.
• Strengthens Grant Competitiveness: Positions the facility at the forefront of correlative, cross-scale imaging – a priority in many funding calls.
• Future-Proofs the Facility: Aligns with the trend toward “imaging across scales” and integrated multimodal workflows.
• Adds Interpretive Value to EM: Makes every EM dataset more meaningful by providing the surrounding context.

Building Smarter, Faster, More Scalable Imaging Labs

The pressure on Core Imaging Labs will only grow as cryo-imaging becomes more integral to disease research and drug discovery. By integrating the SXT-100, lab managers can directly address throughput bottlenecks, sample preparation challenges, and cross-scale correlation gaps – all while adding essential volume context to interpret EM data and enabling targeted imaging in unstained tissue samples.

The result: Faster science, richer insights, and a facility that stays ahead in the rapidly evolving imaging landscape.

About SiriusXT: SiriusXT designs and manufactures the SXT-100, the world’s first commercial, laboratory-scale cryo-soft X-ray microscope. Built to deliver synchrotron-quality imaging directly in the lab, the SXT-100 empowers researchers to visualise the whole structure of intact biological cells and tissues in their near-native state.

Check out our images gallery to learn more about the power of Soft X-ray Tomography!