View source for 2026Fromm LowDose

== Citation ==

Fromm, S.A. and Mattei, S. 2026. LowDoseWizard–rapid and standardised setup of low-dose cryo-TEM imaging in SerialEM. Acta Crystallographica Sec. D. 82, (2026), 990–997.

== Abstract ==

Structure elucidation of biological macromolecules by single-particle cryogenic
electron microscopy (SPA cryo-EM) or cryogenic electron tomography (cryo-
ET) relies on low-dose imaging on cryogenic transmission electron microscopes
(cryo-TEMs). Routine microscope setup remains technically demanding and
can be time-consuming, particularly for inexperienced or infrequent users. We
present LowDoseWizard, a guided workflow implemented in SerialEM that
enables rapid and standardized setup of cryo-TEM imaging conditions. From
minimal user input, the workflow configures microscope optics, camera parameters
and image-shift settings for all low-dose states, and guides the user
through key daily alignment procedures, including beam-shift offset calibration,
objective-lens astigmatism correction and coma-free alignment. The workflow
is organized into modular routines that can be executed sequentially or independently,
while microscope-specific acquisition parameters are defined in
editable configuration files, allowing flexible adaptation to different instruments
without modification of the core scripts. Across user sessions on three microscopes
at EMBL Heidelberg, the complete setup required on average less than
15 min. To assess whether predefined imaging conditions generated by the
workflow are compatible with high-resolution data collection, we acquired
apoferritin data on a 200 kV Glacios and a 300 kV Titan Krios. These datasets
yielded reconstructions at 1.62 and 1.09 A ˚ resolution, respectively, demonstrating
that rapid, guided setup can support near-atomic and atomic-resolution
SPA cryo-EM. LowDoseWizard lowers the barrier to robust cryo-TEM setup,
reduces the time spent on routine parameter selection and alignment, and helps
users focus on sample-specific aspects of data acquisition such as target selection.
The workflow should be particularly valuable in shared instrumentation
environments, where accessibility, reproducibility and efficient microscope use
are critical.

== Keywords ==

== Links ==

https://journals.iucr.org/d/issues/2026/08/00/sor5006/index.html

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