What question did this study set out to answer?

The aim is to enhance 3D correlative light and electron microscopy by improving substrate preparation and registration.

May 21, 2026Methods in microscopyOpen Access

Towards the automation of 3D correlative light and electron microscopy: streamlining substrate preparation and fiducial-free registration

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Randomized trial examines 3D CLEM methods in biological samples, suggesting improved accessibility and efficiency.

The aim is to enhance 3D correlative light and electron microscopy by improving substrate preparation and registration.
Engineered CLEM substrates with surface treatments for better cell adhesion.
Implemented an automated fiducial-free 3D registration pipeline using lipid droplets.
Compared different coatings for EM grids and developed a UV photopatterning prototype.
Achieved an accuracy of below 1 µm in 3D for aligning fluorescence and EM datasets.
Demonstrated reproducibility in confining cells at known coordinates.
Enhanced probability of acquiring useful 3D CLEM datasets per specimen with minimized manual input.

Fuchs et al. (2026) studied this question.

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