{
  "abstract": "In situ electron cryo-tomography (cryo-ET) is a powerful tool for visualising biology inside cells at the molecular scale. The routine application of cryo-ET in tissue samples promises biological insight beyond single cells, but is currently limited by the technical challenge of preparing high quality, electron-transparent specimens from thick (>100 m) biopsies efficiently. Here, we demonstrate that cryogenic femtosecond pulsed laser ablation (cryo-fs-PLA) can accelerate the preparation of vitreous specimens of mammalian brain tissue for cryo-ET. Using cryogenic fluorescence microscopy, regions of interest within high-pressure frozen tissue can be specifically targeted, and cryo-fs-PLA can be employed as a preparative step for serial cryogenic lift-out experiments. We define cryo-fs-PLA parameters and determine ablation rates for two different laser wavelengths, and demonstrate that tilt series collected on lamellae fabricated from sites exposed to cryo-fs-PLA largely maintain their vitrification state. Incorporating cryo-fs-PLA into existing cryo-ET workflows has the potential to unlock the sample preparation of tissues at the throughput necessary for routine in situ cell biology of multicellular samples.",
  "abstract_shown": true,
  "affiliations": [
    "Rosalind Franklin Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "J. L. R. Smith"
    },
    {
      "name": "R. N. Gannon"
    },
    {
      "name": "C. Glynn"
    },
    {
      "name": "J. H. Naismith"
    },
    {
      "name": "J. Filevich"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Grange"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eeawjeqvwtcae.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.28.761815",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.761815v1.full",
  "id": "eeawjeqvwtcae",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.761815v1",
  "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",
      "biochemistry"
    ],
    [
      "openalex",
      "1315|Advanced Electron Microscopy Techniques and Applications"
    ]
  ],
  "openalex": "W7224124183",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.761815v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/eeawjeqvwtcae.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:30:11Z",
      "native_id": "10.64898/2026.10.28.761815",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.28.761815v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1315|Advanced Electron Microscopy Techniques and Applications",
      "subfield": "structural-biology"
    }
  ],
  "title": "Femtosecond pulsed laser ablation for in-tissue electron cryo-tomography",
  "title_text": "Femtosecond pulsed laser ablation for in-tissue electron cryo-tomography",
  "type": "preprint",
  "updated_at": "2026-11-01T00:20:45Z",
  "url": "https://research.draconitic.com/paper/eeawjeqvwtcae",
  "venue": "bioRxiv",
  "versions": []
}