{
  "abstract": "Direct detection of rare nucleic-acid targets without molecular amplification requires specific recognition events to be made observable while remaining distinguishable from nonspecific interactions. Here, we introduce a microbead-based heterodimer assay (MBHA) that converts two-site recognition of single-stranded DNA into spatially resolved, two-color bead-pairing events for direct nucleic acid detection. Two spectrally distinct microbead populations are functionalized with partially double-stranded DNA probes exposing target-binding domains complementary to separate regions of the target. Target-mediated bridging produces heterotypic bead pairs that are classified by fluorescence identity and an interparticle-distance criterion, while residual background is evaluated relative to blank measurements. Under the tested conditions, 166 fM was the lowest target concentration exceeding the blank-derived detection threshold. A sequence-scrambled synthetic non-target DNA remained below threshold across the tested concentration range, and detection at 166 fM was retained in the presence of 1 uM non-target DNA, corresponding to an approximately six-million-fold molar excess. Probe redesign further extended the assay to a second 60-nucleotide synthetic DNA target derived from the SARS-CoV-2 ORF1ab sequence. This proof-of-concept study establishes heterodimer counting as an amplification-free measurement strategy in which rare molecular-recognition events are made directly observable and individually classifiable without increasing target copy number.",
  "abstract_shown": true,
  "affiliations": [
    "LIMMS/CNRS-Institute of Industrial Science"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "S. R. Roy"
    },
    {
      "name": "N. Lobato-Dauzier"
    },
    {
      "name": "J. Mateos"
    },
    {
      "name": "Y. Tauran"
    },
    {
      "name": "A. Brioude"
    },
    {
      "name": "A. Baccouche"
    },
    {
      "name": "T. Fujii"
    },
    {
      "name": "A. J. Genot"
    },
    {
      "name": "S. H. Kim"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7k0p55zrpmz3d.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.28.762408",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762408v1.full",
  "id": "7k0p55zrpmz3d",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762408v1",
  "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",
      "biophysics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762408v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7k0p55zrpmz3d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:30:23Z",
      "native_id": "10.64898/2026.10.28.762408",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762408v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    }
  ],
  "title": "Microbead-Based Heterodimer Assay for Amplification-Free Detection of Single-Stranded DNA",
  "title_text": "Microbead-Based Heterodimer Assay for Amplification-Free Detection of Single-Stranded DNA",
  "type": "preprint",
  "updated_at": "2026-11-03T00:20:31Z",
  "url": "https://research.draconitic.com/paper/7k0p55zrpmz3d",
  "venue": "bioRxiv",
  "versions": []
}