{
  "abstract": "Interleukin-6 (IL-6) is a key inflammatory cytokine involved in numerous physiological and pathological processes, including cancer progression, fibrosis, and immune regulation. Rapid and label-free detection of IL-6 in complex biological environments is challenging due to its small size, which is overshadowed by the presence of large numbers of competing biomolecules. In this work, we develop a method to detect the spectroscopic signature of IL-6 in complex matrices using a nanobodyfunctionalized plasmonic metasurface that acts as a surface-enhanced Raman spectroscopy (SERS) sensor. Machine-learning-based spectral analysis enables identification of subtle molecular signatures of IL-6, despite the presence of competing species. We measured binary protein solutions containing IL-6 and bovine serum albumin (BSA), followed by IL-6-spiked cell culture medium and fibroblastconditioned culture medium. The mixed IL-6/BSA experiments show that elevated IL-6 scores can be recovered even at BSA-to-IL-6 ratios up to 100:1. In cell culture medium, the IL-6 score depends on the concentration and the observed trend deviates from the well-known Langmuir isotherm model. We developed a model that considers IL-6 binding on the nanobodies as a two-site adsorption problem that accounts for the metasurface geometry and steric effects. The model agrees well with the experimental data. Transforming growth factor beta (TGF-β)-stimulated fibroblast samples show a modest shift toward higher IL-6 scores than medium samples without TGF-β stimulation. Our approach is versatile and applicable to analyzing other biomolecules in a complex biological ‘soup’ of molecules and proteins.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Science and Technology",
    "Institute for Nanotechnology",
    "Organ-on-Chip Centre Twente",
    "University of Twente",
    "Vysens B.V."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sharif Zaidouni"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Utku Devamoglu"
    },
    {
      "affs": [
        4
      ],
      "name": "Anouk Mentink"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Séverine Le Gac"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Oluwafemi Stephen Ojambati"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7hrchsexymhmj.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010309/v1",
  "fulltext_url": null,
  "id": "7hrchsexymhmj",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010309/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2504|Gold and Silver Nanoparticles Synthesis and Applications"
    ]
  ],
  "openalex": "W7221672813",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010309/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/7hrchsexymhmj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:24Z",
      "native_id": "10.26434/chemrxiv.15010309",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010309/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:2504|Gold and Silver Nanoparticles Synthesis and Applications",
      "subfield": "materials-polymers"
    }
  ],
  "title": "Finding a small cytokine inside complex biological matrices using nanobody-functionalized plasmonic metasurfaces",
  "title_text": "Finding a small cytokine inside complex biological matrices using nanobody-functionalized plasmonic metasurfaces",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:24Z",
  "url": "https://research.draconitic.com/paper/7hrchsexymhmj",
  "venue": "ChemRxiv",
  "versions": []
}