{
  "abstract": "Online structural characterization during microfluidic lipid self-assembly is important for understanding and controlling the formation of nonlamellar liquid crystalline nanodispersions. Here, we report a 3D-printed, X-ray-compatible hydrodynamic flow-focusing microfluidic chip with variable channel dimensions, integrated with synchrotron small-angle X-ray scattering (SAXS), for position-resolved SAXS-on-chip monitoring of Ca2+-triggered hexosome formation. Hexosomes were produced under continuous flow by mixing ethanolic solutions of docosahexaenoic acid monoglyceride (MAG-DHA), the negatively charged phosphatidylglycerol DOPG, and -tocopherol with Ca2+-containing PIPES buffer. Online SAXS-on-chip measurements detected three Bragg reflections characteristic of the internal inverse hexagonal (H2) phase on a tens-of-milliseconds residence-time scale, revealing rapid structural evolution during microfluidic mixing. Complementary ex situ SAXS identified the DOPG/Ca2+ molar ratio as a key parameter modulating the direct vesicle-to-hexosome transformation and the compactness of the internal H2 nanostructures. Dynamic light scattering showed that the flow-rate ratio modulated nanoparticle size, yielding hexosomes with mean hydrodynamic diameters in the range of approximately 120-175 nm and polydispersity index values down to 0.14 at a total flow rate of 200 {micro}L min-1. Cryo-TEM revealed coexistence of hexosomes and vesicular nanostructures, highlighting morphological heterogeneity, while Coarse-Grained Molecular Dynamics simulations supported a central role of Ca2+-DOPG association in promoting a direct lamellar-H2 phase transition. Overall, this work shows that 3D-printed SAXS-compatible microfluidics can integrate continuous production with online structural characterization, providing a basis for future formulation and process optimization of drug-loaded cubosomes, hexosomes, and related nonlamellar liquid crystalline nanodispersions.",
  "abstract_shown": true,
  "affiliations": [
    "University of Copenhagen"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "Z. Babaie"
    },
    {
      "name": "M. Valerio"
    },
    {
      "name": "F. Schuhmann"
    },
    {
      "name": "M. Dimaki"
    },
    {
      "name": "B. Rezaei"
    },
    {
      "name": "W. Pezeshkian"
    },
    {
      "name": "S. S. Keller"
    },
    {
      "name": "W. E. Svendsen"
    },
    {
      "name": "P. C. T. d. Souza"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Yaghmur"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e87tsf24kesr0.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.31.748233",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748233v1.full",
  "id": "e87tsf24kesr0",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748233v1",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "biophysics"
    ],
    [
      "hal",
      "0.chim"
    ],
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      "hal",
      "0.info"
    ],
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      "hal",
      "1.chim.mate"
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      "hal",
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    ],
    [
      "openalex",
      "2204|Innovative Microfluidic and Catalytic Techniques Innovation"
    ]
  ],
  "openalex": "W7204968769",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748233v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-31",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e87tsf24kesr0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.64898/2026.08.31.748233",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.31.748233v1"
    },
    {
      "first_seen": "2026-10-30T12:17:51Z",
      "native_id": "hal-05787669",
      "source": "hal",
      "url": "https://hal.science/hal-05787669v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:biophysics",
      "subfield": "biophysics"
    },
    {
      "field": "chemistry",
      "origin": "hal:1.chim.mate",
      "subfield": "materials-polymers"
    },
    {
      "field": "chemistry",
      "origin": "hal:1.chim.theo",
      "subfield": "theoretical"
    }
  ],
  "title": "3D Printed X-ray Compatible Microfluidics for Online Characterization of Hexosomes: A Synchrotron SAXS-on-Chip Study with Molecular Dynamics Insights",
  "title_text": "3D Printed X-ray Compatible Microfluidics for Online Characterization of Hexosomes: A Synchrotron SAXS-on-Chip Study with Molecular Dynamics Insights",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:51Z",
  "url": "https://research.draconitic.com/paper/e87tsf24kesr0",
  "venue": "bioRxiv",
  "versions": []
}