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Updated: Jul 2, 2025

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Sample Preparation and Imaging of Exosomes by Transmission Electron Microscopy
Published on: January 4, 2018
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Imaging of Isolated Exosomes by Correlative Microscopy
Şeyda Demir1,2, Esra Erdal3,4, Hüsnü Alper Bagriyanik1,2,4
1Department of Histology and Embryology, Faculty of Medicine.
Summary
Correlative light and electron microscopy (CLEM) challenges exosome imaging. Confocal-scanning electron microscopy (SEM) correlation offers a more applicable method for visualizing these nanoscale vesicles and their clustered arrangements.
Area of Science:
- Biophysics
- Cell Biology
- Nanotechnology
Background:
- Correlative microscopy, particularly correlative light and electron microscopy (CLEM), integrates optical and electron microscopy for comprehensive biological sample analysis.
- CLEM presents significant sample preparation challenges due to the distinct requirements of light and electron microscopy techniques.
- Visualizing nanoscale structures like exosomes (30-150 nm) is difficult due to their small size and low electric charge, hindering the understanding of their morphology and function.
Purpose of the Study:
- To evaluate the efficacy of correlative light and electron microscopy (CLEM) for imaging exosomes.
- To compare the suitability and efficiency of confocal microscopy and scanning electron microscopy (SEM) in combination for nanoscale imaging.
- To investigate the arrangement and morphology of exosomes using advanced correlative imaging techniques.
Main Methods:
- Utilized correlative light and electron microscopy (CLEM) combining confocal microscopy with transmission electron microscopy (TEM) and scanning electron microscopy (SEM).
- Performed a comparative analysis of different CLEM configurations to assess their performance in imaging nanoscale structures.
- Focused on evaluating the specific application of confocal-SEM correlation for exosome visualization.
Main Results:
- Confocal-SEM correlation demonstrated higher applicability for imaging exosomes compared to other tested CLEM approaches.
- Exosomes were observed to form clusters when visualized using the confocal-SEM correlation technique.
- The study provided insights into the high-resolution imaging capabilities of CLEM for nanovesicles.
Conclusions:
- Confocal-SEM correlation is a more suitable method for high-resolution imaging of exosomes.
- The findings reveal that exosomes tend to aggregate in clusters, providing valuable morphological information.
- This research advances the understanding of exosome visualization techniques, crucial for studying their biological roles.

