Skip to content
DraconiticResearch
Search Sources API
197,785 studies31 sourcesUpdated 16 min ago
PreprintCC BY 4.0ChemRxiv

A Blood–Brain Barrier-on-Chip Approaching In Vivo Tightness for Quantitative Ultrasound-Mediated Opening

  • Mathis Martin1,2,3
  • Mame-Diarra Sylla1,2,3
  • Agathe Neukelmance4,5
  • Pascal Dargent3
  • Wladimir Urbach1,2,3
  • Stéphane Desgranges6
  • Chistiane Contino-Pépin6
  • Ayako Yamada4,5
  • Nicolas Taulier3
6 affiliations
  1. 1ENS
  2. 2Université PSL, CNRS, Sorbonne Université, Université de Paris
  3. 3Sorbonne Université,
  4. 4Department of Chemistry, École Normale Supérieure
  5. 5Sorbonne Université, CNRS
  6. 6UPRI
Open at sourcePDFDOICite

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.

Related

  1. Quantitative Ultrasound Perfusion Biomarker: Cross-Modality Validation with Laser Speckle Imaging
    Haowei Tai, Oscar Duran-Garnica, Karen Villarreal +2
    arXivPreprintarXiv licenceFull textBiological & medical physicsarXiv
  2. Quantitative Ultrasound Characterizes Perfusion Trajectories in Healthy and Inflamed Gingival Wound Healing
    Haowei Tai, Oscar Duran-Garnica, Karen Villarreal +2
    arXivPreprintarXiv licenceFull textBiological & medical physicsarXiv
  3. Buccal-Lingual Analysis and Inflammation Tracking in Oral Soft Tissues Using Quantitative Ultrasound: A Preclinical Study
    Daria Poul, Amanda Rodriguez Betancourt, Ankita Samal +6
    arXivPreprintarXiv licenceFull textBiological & medical physicsarXiv
  4. Strict non-tightness of the level-3 quantum bootstrap for a natural three-dimensional Hamiltonian, at an excited level
    Daniel Keren, Ye Zhou
    arXivPreprintarXiv licenceFull textMathematical physicsQuantum physics & quantum informationarXiv
  5. Approaching the limit of quantum clock precision
    Chad C. Nelmes, Emanuel Schwarzhans, Tony J. G. Apollaro +2
    Physical Review ResearchPeer-reviewedCC BY 4.0Atomic, molecular & optical physicsCrossref

Cite

BibTeXRIS
BibTeX
@misc{martin2026bloodbrain,
  title = {{A Blood–Brain Barrier-on-Chip Approaching In Vivo Tightness for Quantitative Ultrasound-Mediated Opening}},
  author = {Mathis Martin and Mame-Diarra Sylla and Agathe Neukelmance and Pascal Dargent and Wladimir Urbach and Stéphane Desgranges and Chistiane Contino-Pépin and Ayako Yamada and Nicolas Taulier},
  howpublished = {ChemRxiv},
  year = {2026},
  month = oct,
  doi = {10.26434/chemrxiv.15009935/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009935/v1},
  note = {CC BY 4.0},
}
RIS
TY  - UNPB
TI  - A Blood–Brain Barrier-on-Chip Approaching In Vivo Tightness for Quantitative Ultrasound-Mediated Opening
AU  - Mathis Martin
AU  - Mame-Diarra Sylla
AU  - Agathe Neukelmance
AU  - Pascal Dargent
AU  - Wladimir Urbach
AU  - Stéphane Desgranges
AU  - Chistiane Contino-Pépin
AU  - Ayako Yamada
AU  - Nicolas Taulier
PY  - 2026
DA  - 2026/10/05
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15009935/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009935/v1
AB  - 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.
ER  -