{
  "abstract": "Cryo-electron tomography (cryo-ET) enables molecular-resolution imaging of intracellular environments, but is constrained by the need to generate electron-transparent sections of the biological specimen and thus a limited imaging volume. To alleviate such limitations, we present a multiscale correlative workflow that links cryo-confocal fluorescence microscopy (cryo-FLM), cryo-focused ion beam-scanning electron microscopy (cryo-FIB-SEM) volume imaging (cryo-vEM), and cryo-FIB serial lamellae lift-out for cryo-ET in high-pressure frozen voluminous specimens. An integral part of this workflow is a sample holder that preserves specimen orientation across instruments, reduces manual handling, and overcomes stage-tilt limitations in cryo-FIB-SEM hardware. Applied to vitrified colorectal cancer organoids, we demonstrate that this workflow enables fluorescence-guided site preparation for cryo-vEM, which provides biological context beyond the limited field of view of cryo-ET, and targeted lift-out for fabrication of multiple lamellae from defined regions of interest. The reconstructed tomograms reveal subcellular architecture and cell-cell interfaces. This workflow establishes a modular methodological framework for continuum-resolution cryogenic imaging of complex 3D biological specimens.",
  "abstract_shown": true,
  "affiliations": [
    "European Molecular Biology Laboratory"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "E. D'Imprima"
    },
    {
      "name": "E. Zagoriy"
    },
    {
      "name": "S. Mimietz-Oekler"
    },
    {
      "name": "R. Kirmse"
    },
    {
      "name": "A. Hallady"
    },
    {
      "name": "P. N. Mbonu"
    },
    {
      "name": "P. Ronchi"
    },
    {
      "name": "M. Jechlinger"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Mahamid"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/24m9edx6b72p1.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.14.759080",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.14.759080v1.full",
  "id": "24m9edx6b72p1",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.14.759080v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "1315|Advanced Electron Microscopy Techniques and Applications"
    ]
  ],
  "openalex": "W7222659798",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.14.759080v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/24m9edx6b72p1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:04Z",
      "native_id": "10.64898/2026.10.14.759080",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.14.759080v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Workflow and instrumentation for multiscale correlative imaging in voluminous cryogenic specimens",
  "title_text": "Workflow and instrumentation for multiscale correlative imaging in voluminous cryogenic specimens",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:04Z",
  "url": "https://research.draconitic.com/paper/24m9edx6b72p1",
  "venue": "bioRxiv",
  "versions": []
}