{
  "abstract": "Telomere length is a biomarker of aging, cancer and telomeropathies, with some of the strongest health-related associations occurring at the extremes of the telomere-length spectrum. Critically short telomeres can drive chromosome instability, cellular stress and senescence, yet conventional assays largely provide population-average measurements that obscure these biologically important molecules, and the underlying heterogeneity of individual chromosome ends. In addition, amplification bias associated with highly repetitive telomeric sequences and inter-laboratory variability can limit measurement reproducibility. Although emerging technologies provide higher-resolution analyses, they often require high DNA input, specialized sample preparation, or complex instrumentation and bioinformatic tools, restricting broader adoption. Here, we present a high-throughput single-molecule platform that overcomes these barriers through an automated, user-friendly nanoscale imaging workflow compatible with standard genomic DNA preparations. The method combines a unique dual CRISPR-Cas9 telomere boundary labeling strategy with amplification-free magnetic-bead-based enrichment, preserving the native telomere-length distribution while minimizing representation bias. Using only 500 ng of input DNA and 2–4 h of hands-on processing, the assay accurately resolves intact telomeres spanning ~50 bp to >50 kb within the same sample, enabling simultaneous characterization of the full telomere-length spectrum. It also demonstrates high reproducibility across technical replicates and independent operators (ICC up to 0.90). Validation in telomere-length models, replicative aging systems, and clinical biospecimens, together with subtelomeric barcoding for chromosome-arm assignment, establishes a scalable platform for chromosome-resolved telomere profiling, biomarker development, and future clinical implementation in aging, cancer, and telomere biology.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "Collen Jackson-Cook"
    },
    {
      "name": "Lilia Gheghiani"
    },
    {
      "name": "Andrey Mikheykin"
    },
    {
      "name": "Dylan Van Laeken"
    },
    {
      "name": "Daniel Guest"
    },
    {
      "name": "Kellie Archer"
    },
    {
      "name": "Harold Riethman"
    },
    {
      "name": "Jason Reed"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e0y08rh9zgx1z.bib",
  "cited_by": 0,
  "doi": "10.21203/rs.3.rs-11283393/v1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13734252/",
  "id": "e0y08rh9zgx1z",
  "issns": [
    "2693-5015"
  ],
  "landing_url": "https://doi.org/10.21203/rs.3.rs-11283393/v1",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1307|Telomeres, Telomerase, and Senescence"
    ]
  ],
  "openalex": "W7223874463",
  "pdf_url": "https://www.researchsquare.com/article/rs-11283393/latest.pdf",
  "pmcid": "PMC13734252",
  "pmid": "42990780",
  "published": "2026-10-28",
  "publisher": "American Journal Experts",
  "ris": "https://research.draconitic.com/paper/e0y08rh9zgx1z.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:53Z",
      "native_id": "PMC13734252",
      "source": "pmc",
      "url": "https://doi.org/10.21203/rs.3.rs-11283393/v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Telomeres, Telomerase, and Senescence",
      "subfield": "cell-biology"
    }
  ],
  "title": "A high-throughput nanoscale imaging platform for direct visualization and rapid measurement of telomeres at single-molecule resolution",
  "title_text": "A high-throughput nanoscale imaging platform for direct visualization and rapid measurement of telomeres at single-molecule resolution",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:53Z",
  "url": "https://research.draconitic.com/paper/e0y08rh9zgx1z",
  "venue": "Research Square",
  "versions": []
}