{
  "abstract": "Protein abundance alone does not capture the molecular diversity generated by protein processing and post-translational modification, yet most single-cell protein assays do not resolve these proteoform states. Here, we develop RCAmp-scWB, a post-separation amplification strategy that performs rolling-circle amplification directly within the polyacrylamide gel after single-cell protein electrophoresis. Reaction-transport modeling identifies a balance between reagent access and confinement of the template-associated amplification product that supports signal amplification while retaining the electrophoretically encoded spatial readout. Using purified protein standards, RCAmp-scWB produced a 4.0-7.8-fold steeper concentration-response slope than conventional single-cell western blotting. Across six human cancer cell lines, RCAmp-scWB quantified protein abundance and resolved distinct Vimentin and PD-L1 proteoform states whose relative abundance and single-cell distributions were not captured by total protein measurements alone. Extension to individual small extracellular vesicles further revealed source-dependent shifts in Vimentin proteoform composition despite comparatively similar abundance of one major Vimentin species. By separating electrophoretic molecular discrimination from signal amplification, RCAmp-scWB enables proteoform-resolved analysis of heterogeneous cells and small extracellular vesicles.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": "2609.36251",
  "author_total": 17,
  "authors": [
    {
      "name": "Luyao Zhao"
    },
    {
      "name": "Yanjun Yang"
    },
    {
      "name": "Yaochao Zheng"
    },
    {
      "name": "Yuhao Zhang"
    },
    {
      "name": "Zhengfu Huang"
    },
    {
      "name": "William Teng"
    },
    {
      "name": "Lucas Yatcyshyn"
    },
    {
      "name": "Jiahwei Cheong"
    },
    {
      "name": "Jonathan Arnold"
    },
    {
      "name": "Jin Xie"
    },
    {
      "name": "Kenan Song"
    },
    {
      "name": "Xianqiao Wang"
    },
    {
      "name": "Yiping Zhao"
    },
    {
      "name": "Xianyan Chen"
    },
    {
      "name": "Yao Yao"
    },
    {
      "name": "Leidong Mao"
    },
    {
      "name": "Yang Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4n5zd5wn05gk1.bib",
  "cited_by": 0,
  "doi": "10.48550/arxiv.2609.36251",
  "fulltext_url": null,
  "id": "4n5zd5wn05gk1",
  "issns": [],
  "landing_url": "https://arxiv.org/abs/2609.36251",
  "language": null,
  "licence": "LicenseRef-arXiv-nonexclusive-1.0",
  "licence_label": "arXiv licence",
  "licence_source": "article",
  "licence_url": "http://arxiv.org/licenses/nonexclusive-distrib/1.0/",
  "metadata_licence": "CC0-1.0",
  "native_subjects": [
    [
      "arxiv",
      "q-bio.QM"
    ],
    [
      "openalex",
      "1607|Advanced Proteomics Techniques and Applications"
    ]
  ],
  "openalex": "W7214937989",
  "pdf_url": "https://arxiv.org/pdf/2609.36251",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4n5zd5wn05gk1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:36Z",
      "native_id": "2609.36251",
      "source": "arxiv",
      "url": "https://arxiv.org/abs/2609.36251"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "arxiv:q-bio.QM",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Gel-Confined Rolling-Circle Amplification Enables Sensitive Single-Cell Proteoform Analysis",
  "title_text": "Gel-Confined Rolling-Circle Amplification Enables Sensitive Single-Cell Proteoform Analysis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:36Z",
  "url": "https://research.draconitic.com/paper/4n5zd5wn05gk1",
  "venue": "arXiv",
  "versions": []
}