Exploring revolutionary imaging techniques that transform our understanding of materials from atomic to macroscopic scales
Imagine being able to zoom inside a human cell to see individual proteins at work, then travel through the nanostructure of a battery material, and finally visualize microscopic cracks in an airplane wing—all in stunning three-dimensional detail.
This isn't science fiction; it's the power of advanced tomography, a revolutionary imaging technique that has transformed our ability to see and understand the intricate architecture of inorganic, organic, and biological materials.
Tomography, derived from the Greek words "tomos" (slice) and "graphia" (describing), allows scientists to reconstruct the 3D structure of objects without physically cutting them open. While most people are familiar with medical CT scans used in hospitals, advanced tomography techniques in research laboratories have reached unprecedented levels of precision, now revealing everything from atomic arrangements in metals to the molecular machinery inside living cells.
Visualize materials at the atomic level with unprecedented clarity and precision.
Bridge the gap between nanometer and millimeter scales in a single workflow.
Study materials and biological samples in their native environments.
At its core, tomography is based on a simple but powerful principle: by collecting multiple two-dimensional projections of an object from different angles, we can mathematically reconstruct its three-dimensional structure. The mathematical foundation for this approach has been known for almost a century, but technological limitations prevented its immediate implementation 1 .
Collect 2D images from multiple angles (typically 50-150 images)
Align images using fiducial markers as reference points
Apply numerical algorithms to reconstruct 3D intensity map
Partition into segments for quantitative analysis
| Technique | Resolution | Penetration Depth | Primary Applications | Key Advantage |
|---|---|---|---|---|
| X-ray Tomography | 10s-1000s nm | Bulk samples | Materials science, engineering | Large penetration depth for bulk samples |
| Electron Tomography | Sub-nm to nm | Thin samples | Nanomaterials, biology | Extremely high spatial resolution |
| Cryo-ET | Molecular level | Cellular samples | Structural biology | Reveals molecular architecture in near-native state |
| PET/CT | Organ level | Whole body | Medical diagnostics, oncology | Combines metabolic and structural information |
The expansion of tomography-compatible imaging modes has enabled investigations of the widest possible range of materials, from molecular assemblies in their native solution environment to high-atomic-number nanocomposites 1 .
Goes beyond conventional imaging by incorporating spectroscopic techniques like electron energy-loss spectroscopy (EELS) and energy dispersive x-ray (EDX) spectroscopy.
These provide not just 3D structural information but direct data on chemical and physical properties at the nanoscale.
Represents the ultimate frontier in resolution with methods that demonstrate sub-nanometer resolution imaging of crystalline lattice planes.
Scientists have developed powerful approaches that combine discrete tomography with quantitative high-angle annular dark-field scanning transmission electron microscopy imaging 1 .
Involves rapidly freezing biological samples in vitreous ice to preserve their native structure, then imaging them using transmission electron microscopy at different tilt angles.
Cryo-ET is emerging as a technique for directly visualizing macromolecular associations and organization in native cells, providing unprecedented insights into cellular architecture 4 .
Combine the strengths of different modalities—PET providing metabolic information and CT offering anatomical context—to deliver more comprehensive data than either could alone 2 .
Recent innovations include PET-enabled Dual-Energy CT, which uses PET scan data to create a second, high-energy CT image that provides clearer pictures and more detailed information 3 .
To understand how these advanced techniques work in practice, let's examine a typical cryo-electron tomography experiment designed to visualize the internal structures of a mammalian cell.
Cells are grown on specialized EM grids and rapidly frozen using liquid ethane to preserve them in a near-native, vitreous state without forming damaging ice crystals.
The frozen samples are thinned using a focused ion beam under cryo-conditions to create electron-transparent lamellas (typically 100-200 nm thick).
The thinned sample is imaged in a transmission electron microscope maintained at cryogenic temperatures. A series of 2D projection images are collected by tilting the specimen.
Acquired tilt series are aligned and computationally reconstructed into a 3D volume. Different cellular components are identified and segmented.
| Step | Key Procedures | Purpose | Tools/Techniques |
|---|---|---|---|
| Sample Prep | Rapid freezing, FIB milling | Preserve native structure, create thin section | Vitrification, cryo-FIB |
| Data Acquisition | Tilt series collection | Capture 2D projections from multiple angles | Cryo-TEM, automated software |
| Reconstruction | Alignment, back-projection | Generate 3D volume from 2D images | Computational algorithms |
| Analysis | Segmentation, averaging | Interpret and enhance structural details | Manual/automated tools, sub-tomogram averaging |
A successful cryo-ET experiment reveals the detailed architecture of cellular components in their native context. Unlike other techniques that require isolating components, cryo-ET captures molecular machines at work within the crowded cellular environment.
Researchers can visualize how ribosomes translate mRNA into proteins, how mitochondria generate energy, and how the cytoskeleton provides structural support—all in 3D.
The resolution achieved through these methods typically reaches 2-4 nm for individual tomograms, sufficient to identify major cellular components and their spatial relationships. When combined with sub-tomogram averaging, the effective resolution can approach sub-nanometer levels, allowing researchers to build atomic models of macromolecular complexes 4 .
Advanced tomography relies on specialized reagents and materials tailored to specific imaging techniques and sample types.
| Reagent/Material | Function | Application Examples |
|---|---|---|
| Radiotracers (FDG) | Metabolic labeling | PET/CT scans for cancer detection 2 |
| Cryo-protectants | Prevent ice crystal formation | Cryo-ET of biological samples 4 |
| Fiducial Markers | Reference points for image alignment | Electron tomography of nanomaterials 1 |
| Immunofluorescence Reagents | Specific protein labeling | Array tomography for protein localization 8 |
| Contrast Agents | Enhance tissue differentiation | Dual-energy CT for cancer imaging 3 |
| Positron-Emitters (C-11, F-18) | Source of gamma rays for detection | PET radiotracer development 5 |
The development of new radiotracers continues to expand the possibilities of PET imaging. Researchers like Dr. Victor Pike and his team are creating novel radioactive reagents such as [11C]fluoroform that serve as versatile building blocks for synthesizing new types of radiotracers 5 .
These advancements open possibilities for imaging a broader range of biological processes, including enzymes and proteins implicated in Alzheimer's disease and harmful inflammatory processes.
Advanced tomography techniques have fundamentally transformed our ability to explore and understand the three-dimensional architecture of matter across scales—from individual atoms to entire organisms.
As these technologies become more accessible and integrated, tomography promises to reveal ever deeper insights into the building blocks of our world, advancing knowledge from the fundamental sciences to clinical applications that directly improve human health.
The ability to visualize the whole system intact with low resolution and then sequentially zoom in with increasing spatial resolution promises new paradigms for interrogating not only static systems but also systems perturbed or evolving over time 1 .