{
  "abstract": "The blood-brain barrier (BBB) remains one of the greatest obstacles to the treatment of neurological diseases, preventing the delivery of nearly all large therapeutics and most small molecules to the brain. Although ultrasound-activated microbubbles offer a promising strategy for transient BBB opening, quantitative in vitro models capable of reproducing physiological barrier properties while allowing controlled ultrasound studies remain scarce. Here, we report a human BBB-on-chip that combines near-physiological barrier tightness with realtime quantitative permeability measurements under ultrasound exposure. We identify the key physical parameters governing barrier formation, demonstrating that microenvironment geometry and hydrogel confinement play a decisive role in establishing a functional endothelial barrier. The optimized platform exhibits permeability coefficients for 10 and 70 kDa dextran that approach in vivo values despite relying on a simple endothelial monoculture under static conditions. To quantitatively characterize barrier integrity, we compare three permeability formulations commonly used in the literature and introduce a complementary impermeability index describing barrier dynamics. Finally, we demonstrate that ultrasoundactivated microbubbles increase barrier permeability by more than sixfold, enabling the extravasation of fluorescent tricaprylin nanodroplets into the hydrogel compartment.",
  "abstract_shown": true,
  "affiliations": [
    "ENS",
    "Université PSL, CNRS, Sorbonne Université, Université de Paris",
    "Sorbonne Université,",
    "Department of Chemistry, École Normale Supérieure",
    "Sorbonne Université, CNRS",
    "UPRI"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Mathis Martin"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Mame-Diarra Sylla"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Agathe Neukelmance"
    },
    {
      "affs": [
        2
      ],
      "name": "Pascal Dargent"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Wladimir Urbach"
    },
    {
      "affs": [
        5
      ],
      "name": "Stéphane Desgranges"
    },
    {
      "affs": [
        5
      ],
      "name": "Chistiane Contino-Pépin"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Ayako Yamada"
    },
    {
      "affs": [
        2
      ],
      "name": "Nicolas Taulier"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/edt4c6dxb4rbz.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15009935/v1",
  "fulltext_url": null,
  "id": "edt4c6dxb4rbz",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009935/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": [
    [
      "hal",
      "0.phys"
    ],
    [
      "hal",
      "1.phys.phys"
    ],
    [
      "hal",
      "2.phys.phys.phys-bio-ph"
    ],
    [
      "openalex",
      "2808|Barrier Structure and Function Studies"
    ]
  ],
  "openalex": "W7220473944",
  "pdf_url": "https://hal.science/hal-05799122/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-05",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/edt4c6dxb4rbz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.26434/chemrxiv.15009935",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009935/v1"
    },
    {
      "first_seen": "2026-10-30T12:17:57Z",
      "native_id": "hal-05799122",
      "source": "hal",
      "url": "https://hal.science/hal-05799122v1"
    }
  ],
  "subjects": [
    {
      "field": "physics",
      "origin": "hal:2.phys.phys.phys-bio-ph",
      "subfield": "biological-medical"
    }
  ],
  "title": "A Blood–Brain Barrier-on-Chip Approaching In Vivo Tightness for Quantitative Ultrasound-Mediated Opening",
  "title_text": "A Blood–Brain Barrier-on-Chip Approaching In Vivo Tightness for Quantitative Ultrasound-Mediated Opening",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:57Z",
  "url": "https://research.draconitic.com/paper/edt4c6dxb4rbz",
  "venue": "ChemRxiv",
  "versions": []
}