ArticleProtein science : a publication of the Protein Society2024
The myth of high-resolution liquid phase biological electron microscopy.
Article in Protein science : a publication of the Protein Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed.
- Ultrathin liquid cells for microsecond time-resolved cryo-EM.Nature communications · 2026Article
- Validation of 3D cryoEM single-particle reconstruction correctness and handedness with Ewald's sphere correction.Structural dynamics (Melville, N.Y.) · 2025Article
- Validation of 3D cryoEM single particle reconstruction correctness and handedness with Ewald's sphere correction.bioRxiv : the preprint server for biology · 2025Article
- Liquid Phase Biological Electron Microscopy: Many Published Results and Claimed Benefits Are Fantasy, Not Fact.Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada · 2025Article
- Extending the reach of single-particle cryoEM.Current opinion in structural biology · 2025Review
- The myth of high-resolution liquid phase biological electron microscopy.Protein science : a publication of the Protein Society · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
Abstract
Cryo-electron microscopy (cryo-EM) has transformed structural biology over the past 12 years, with it now being routine rather than exceptional to reach a near-atomic level of resolution for proteins and macromolecular complexes. Samples are immobilized by vitrification and this sample can be maintained at liquid nitrogen temperatures in the vacuum of the electron microscope with negligible sublimation. Due to the low electron doses needed to avoid radiation damage, averaging over tens of thousands to hundreds of thousands of particle images is used to achieve a high signal-to-noise ratio. An alternative approach has been proposed where samples are at room temperature in the liquid state, maintained in the vacuum of the electron microscope by thin film enclosures that are relatively transparent to electrons while preventing evaporation of the liquid. A paper has argued that using this liquid-phase approach, higher resolution (3.2 Å) can be achieved than using cryo-EM (3.4 Å) when imaging and reconstructing adeno-associated virus particles. I show here that these assertions are untrue, and that basic principles in mathematics and physics would need to be violated to achieve the stated resolution in the liquid state. Thus, high resolution liquid phase EM of macromolecules remains science fiction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.