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Explore cellular ultrastructure with ultra-high-resolution microscopy
Transmission electron microscopy makes it possible to visualize the internal structure of cells, organelles, and macromolecules, providing insights into their organization and function. It is a key technology for researchers across all fields of life sciences interested in ultrastructural analyses and morphological studies, as well as pathologists looking for disease-related changes in cell and tissue structure.
The Thermo Scientific Talos 12 TEM makes it easy to navigate large samples, find regions of interest, and set up unattended batch acquisition of multiple tile sets for high-resolution, multi-scale imaging of intracellular organelles and structures. With the context intact, navigating the sample is easy and intuitive, even for new users.
What will you discover with nanoscale imaging using Talos 12 TEM?
From muscles to macrophages, imaging resin-embedded tissues in high resolution enables ultrastructural observation in all fields of biology.
Resin-embedded tissues imaged by TEM at various magnifications.
Talos 12 TEM as a pathology imaging system
The Talos 12 TEM delivers crisp, high-contrast, multi-scale images to capture the structural details and context needed to understand cell and tissue pathologies, from viral or microorganism infections to organ anomalies and cancer. Streamlined workflows deliver results in less time for microscopists examining renal pathology to neuromuscular pathology, peripheral neuropathy, and more. These workflows also make it possible for multiple people to use one instrument, helping newer users easily collect data and offering sophisticated controls for experienced users.
Example workflow in renal pathology: glomerular basement membrane (GBM) examination. Images courtesy of the Department of Renal Pathology. Brigham and Women’s Hospital, USA.
Expand your cell and tissue imaging with advanced Talos 12 TEM applications
Correlative light and electron microscopy
Gain more insights through a combination of imaging technologies. CLEM combines the strengths of both techniques: light microscopy offers the ability to use fluorescent markers to label specific proteins or structures, whereas electron microscopy provides high-resolution, detailed images of cellular ultrastructure down to the nanometer scale.
CLEM with the Talos 12 TEM is streamlined with Thermo Scientific Maps 3 Software, yielding a more comprehensive understanding of biological samples.
Maps 3 Software for correlative light microscopy
Tomography for 3D spatial relationships
3D visualization with tomography provides detailed insights into the organization of cellular structures and macromolecular complexes at nanometer resolution. Gain detailed structural information into spatial relationships of cellular components, such as organelles, virus particles, and protein complexes.
Tomography with the Talos 12 TEM is powered by Thermo Scientific Tomography 5 Software along with AI deep-learning-based segmentation in Thermo Scientific Amira Software.
3D tomography of cilia in a resin-embedded lung tissue section
EDS elemental analysis for compositional understanding
Analyze the distribution of elements in cellular structures, tissues, and biominerals with the addition of energy-dispersive X-ray spectroscopy.
Powered by Thermo Scientific Velox Software, EDS elemental analysis can be leveraged from quick surface scans down to the analysis of individual atoms. As EDS is heavily used by materials science and geoscience researchers, it can be a valuable addition on Talos 12 TEMs in multi-user facilities that are shared across multiple departments. Expand EDS analysis to large-area tile sets with Maps 3 Software or in 3D with Tomography 5 Software.
EDS analysis of Magnetospirillum gryphiswaldense. Sample courtesy of Prof. Dr. Dirk Schüler, University of Bayreuth, Germany
Structural biology with the Talos 12 TEM
Structural biology examines the architecture of biological macromolecules to better understand how they function. TEM is a key technology for researchers in this field and offers different techniques.
The Talos 12 TEM provides scientists with a lower point of entry for visualizing protein complexes and cellular structures either with negative stain imaging or under cryogenic conditions. Additionally, the Talos 12 TEM can be used to optimize sample preparation for single particle analysis to reduce time to results for high-resolution 3D protein structure determination.
Negative stain imaging for straightforward and efficient 2D imaging
Negative stain imaging is a simple and efficient TEM technique used by structural biologists to examine proteins in 2D.
Examine nanoparticles, protein complexes, viruses, bacteria, and cellular components in high contrast with negative stain imaging.
This simple and efficient technique provides clear images of biological specimens to study their structure and function.
Negative stain image of bacteriophage at different magnifications
Optimizing cryo-EM sample preparation for single particle analysis
Cryo-EM is a form of electron microscopy in which samples are rapidly frozen to preserve their natural structure without the need for fixation or staining. Single particle analysis is a cryo-EM technique used to determine the 3D structure of macromolecules, such as proteins and complexes, at high resolution. This development has enabled the 3D analysis of complexes that do not crystallize (and therefore are inaccessible to X-ray crystallography) such as ribosomes and proteasomes, as well as membrane proteins, viruses, and nanoparticles.
Proper sample preparation is crucial for obtaining optimal single particle analysis data. Well-prepared samples help preserve native structures, minimize artifacts, and provide a homogeneous, well-distributed sample with diverse orientations, all of which are essential for accurate and high-resolution 3D reconstruction.
The Talos 12 TEM is designed to quickly assess the stability, homogeneity, and concentration of purified samples, either with negative stain imaging or under cryogenic conditions. Ice thickness, particle density, air-water interface artifacts, and the preferred orientation of particles can be adjusted. Optimized sample conditions will lead to improved results and shorter time to structure from the subsequent single particle analysis data collection, performed with either the Talos 12 TEM itself or using a higher kV cryo-TEM.
Sample considerations for improving single particle analysis data collection for faster time to results and higher-resolution data. The top panel reviews different areas of consideration including particle coverage, air/water interface, protein aggregation and ice thickness. The bottom panel shows a detergent screen with (A) FOM, (B) DM, (C) Tween 20, (D) CTAB, (E) OG and (F) CHAPS. (F) yields the best conditions for single particle analysis data collection.
Single particle analysis data collection
The Talos 12 TEM features automated single particle analysis data collection powered by Thermo Scientific EPU Software. The instrument’s integrated Thermo Scientific Ceta Camera is also optimized for the low doses used in single particle analysis, meaning that the Talos 12 TEM can easily resolve 3D structures of protein complexes at up to ~6 Å. At this resolution, individual protein subunits can be determined along with their arrangement and interactions. Combined with the optional Thermo Scientific Falcon C Direct Electron Detector, it can expand these capabilities, providing a standalone single particle analysis solution for a range of target proteins.
Single particle analysis examples. Left: AAV-2 capsid with achieved resolution of 6.8 Å. Right: Apoferritin with achieved resolution of 5.7 Å.
3D imaging of cellular structures and nanoparticles
The Talos 12 TEM can be equipped with Tomography 5 Software for automated tilt-series acquisition using integrated workflows. Search map acquisition enables mapping of entire grid squares using medium magnification, offering increased data-collection throughput and improved navigational accuracy. Several regions of interest can then be identified for automatic multi-site batch acquisition of 3D data for tomography.
Off-axis multi-shot acquisition significantly enhances throughput. This feature allows several tomogram positions to be recorded with only one focus and tracking area, thereby streamlining the data acquisition process and increasing efficiency. The dose-symmetric acquisition scheme ensures optimal electron dose distribution for high resolution sub-tomogram averaging.
AI-powered segmentation with Amira Software reveals fine details of proteoliposome architecture. Sample courtesy of Dr. Sara García-Linares and Dr. Alvaro Martínez-del-Pozo, Complutense University of Madrid, Spain, and Dr. Jaime Martín-Benito Romero CNB-CSIC, Spain.
Lipid nanoparticle characterization with cryo-EM
Optimizing drug delivery systems
Nanoparticle-based drug delivery systems have emerged as a powerful tool in drug development of gene therapy vectors. Among these, lipid nanoparticles (LNPs) stand out due to their unique properties, including high surface area, tunable size, and the ability to encapsulate and deliver therapeutic agents. Regulatory authorities, including the US FDA and the European Medicines Agency, emphasize the analysis of key morphological features to ensure the efficacy and quality of nanoparticle- and viral-vector-based therapeutics.
The Talos 12 TEM delivers the data for the analysis of critical quality attributes (CQAs), including accurate size and shape, encapsulation efficiency assessment of RNA loading and distribution, batch-to-batch consistency, as well as nanostructural insights and process optimizations.
Cryo-EM is the most widely used method for LNP analysis, having advantages in accuracy, direct visualization of size, shape, lamellarity, and 2D/3D morphology, as well as the ability to determine surface properties at high resolution and at near-native conditions, regardless of cargo or formulation.
CQA analysis of drug delivery vectors
Achieving statistical significance in CQA assessment requires the analysis of large datasets with numerous particles.
The Talos 12 TEM, optimized for high-throughput nanoparticle imaging, paired with AI-enabled Amira 3D Software for semiautomated image processing, delivers a streamlined workflow for fast, accurate, and reproducible LNP characterization.
Semi-automating LNP and AAV characterization
High-throughput data acquisition with the Talos 12 TEM, equipped with EPU Software and combined with AI-based image analysis in Amira 3D Software, can automate image analysis workflows and enhance the precision and efficiency of nanoparticle characterization. Tailored workflows for both LNP and AAV analysis provide detailed insights and reduce the time and human error associated with traditional methods.
Beyond basic metrics such as shape, size, and morphology, Amira 3D Software enables a wide range of CQA analyses through customizable scripts. Tailor investigations to specific research needs, ensuring comprehensive and precise evaluations of LNPs. Whether it’s assessing particle distribution, surface characteristics, or internal architecture, Amira 3D Software stands out as a powerful and versatile tool in the field of nanoparticle research.
Cryo-TEM images of LNPs were analyzed with the described workflow. Particle shape (elongation), surface area, and diameter were calculated for the particle population of more than 600 LNPs. The full analysis process, including the generation of the AI segmentation model, was performed in approximately one hour.
Cryo-TEM images of AAVs were analyzed with the described workflow. Particle shape (elongation), diameter, and the number of filled and empty particles were calculated for the population of more than 300 AAVs. The full analysis process, including the generation of the AI segmentation model, was performed in approximately 12 hours.
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