{
  "abstract": "Achieving thin ice with optimal thickness is a prerequisite for successful cryo-EM analysis of embedded macromolecules. Despite decades of effort, precise control of ice thickness in cryo-EM remains a major challenge. Here we reveal that the intrinsic instability of sub-100-nm liquid film, a previously overlooked determinant before vitrification, plays a critical role in controlling ice thickness. We found that well-designed graphene reservoirs can confine liquid film to an optimal thickness and overcome the limitations posed by liquid film instability, achieving precise control of ice thickness with robust reproducibility and large-area uniformity. These graphene reservoirs demonstrate superior liquid retention capabilities than conventional techniques, enabling tunable ice thickness through reservoir depth modulation. Moreover, this approach yields uniform confined ice in graphene sandwiches with controllable thickness and high efficiency, facilitating cryo-EM imaging of a broad range of macromolecule particles with high contrast, reduced motion and improved orientations for more robust high-resolution reconstruction.",
  "abstract_shown": true,
  "affiliations": [
    "Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China",
    "Ministry of Education Key Laboratory of Protein Sciences, Beijing Frontier Research Center for Biological Structures, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China",
    "State Key Laboratory for Turbulence and Complex System, School of Mechanics and Engineering Science, Peking University, Beijing, China",
    "School of Biological Sciences, The University of Hong Kong, Hong Kong, China",
    "Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China",
    "Beijing Graphene Institute (BGI), Beijing, China",
    "Key Laboratory for the Physics and Chemistry of Nanodevices and Center for Carbon-based Electronics, School of Electronics, Peking University, Beijing, China",
    "Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China",
    "Institute of Bio-Architecture and Bio-Interactions, Shenzhen Medical Academy of Research and Translation, Shenzhen, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Liming Zheng",
      "orcid": "0009-0008-3174-4922"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiling Song",
      "orcid": "0009-0007-9297-584X"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaole Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Jiacong Cao"
    },
    {
      "affs": [
        1
      ],
      "name": "Jie Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhengni Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Chenhui Zhang"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Weiyu Sun"
    },
    {
      "affs": [
        5
      ],
      "name": "Buhang Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoyin Gao"
    },
    {
      "affs": [
        6
      ],
      "name": "Haonan Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Junhao Yang"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Yu Xu"
    },
    {
      "affs": [
        5
      ],
      "name": "Luzhao Sun",
      "orcid": "0000-0003-0518-0744"
    },
    {
      "affs": [
        2
      ],
      "name": "Zhaohe Dai",
      "orcid": "0000-0002-5205-089X"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiaoding Wei",
      "orcid": "0000-0002-5173-4923"
    },
    {
      "affs": [
        3
      ],
      "name": "Nan Liu",
      "orcid": "0000-0003-4102-2428"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Hailin Peng",
      "orcid": "0000-0003-1569-0238"
    },
    {
      "affs": [
        1
      ],
      "name": "Hong-Wei Wang",
      "orcid": "0000-0001-9494-8780"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ccj37xeefpeyr.bib",
  "cited_by": 0,
  "doi": "10.1038/s41592-026-03244-1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736671/",
  "id": "ccj37xeefpeyr",
  "issns": [
    "1548-7091",
    "1548-7105"
  ],
  "landing_url": "https://doi.org/10.1038/s41592-026-03244-1",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "1315|Advanced Electron Microscopy Techniques and Applications"
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  "openalex": "W7214283605",
  "pdf_url": "https://www.nature.com/articles/s41592-026-03244-1.pdf",
  "pmcid": "PMC13736671",
  "pmid": "42791405",
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ccj37xeefpeyr.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:04Z",
      "native_id": "PMC13736671",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41592-026-03244-1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1315|Advanced Electron Microscopy Techniques and Applications",
      "subfield": "structural-biology"
    }
  ],
  "title": "Control of ice thickness in cryo-EM via confinement",
  "title_text": "Control of ice thickness in cryo-EM via confinement",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:04Z",
  "url": "https://research.draconitic.com/paper/ccj37xeefpeyr",
  "venue": "Nature Methods",
  "versions": []
}