@article{46612073-5a57-4bd8-afe2-c6c8599a6ae2,
  abstract     = {{<p>Precise mapping of structural heterogeneity at the sub-10 nm scale is pivotal for rational nanoparticle design, yet conventional analytical workflows remain inadequate. Here we integrate dilution-controlled asymmetric flow field-flow fractionation (AF4) with small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS) to interrogate ellipsoidal solid–liquid lipid nanoparticles (LNPs). The dilution-controlled AF4 mode amplifies scattering contrast, enabling robust, shape-resolved analysis across entire elution profiles. Coupling AF4 to SANS in D<sub>2</sub>O further sharpens resolution for the smallest fractions by reducing particle diffusion through increased solvent viscosity. Comparative sizing shows that SAXS/SANS accurately capture primary particles down to ∼5 nm, whereas multi-angle light scattering chiefly detects loosely associated aggregates. Morphology profiling reveals that surfactant identity governs particle shape, polydispersity, and overall architecture. Joint SAXS/SANS modeling uncovers a 2–3 nm polar shell enveloping an internal core–shell morphology. Together, these insights refine our understanding of LNP size, morphology and drug localization and establish dilution-controlled AF4-SAXS/SANS as a high-resolution platform for dissecting complex nanoparticle systems relevant to biomedical applications.</p>}},
  author       = {{Bittrich, Eva and Boye, Susanne and Van Niekerk, Zanelle and Stanvliet, Zahn and Porfetye, Arthur and Herranz-Trillo, Fátima and Bolinsson, Hans and Gaydarova, Stefaniya and Tzachev, Christo and Martel, Anne and Nilsson, Lars and Schweins, Ralf and Lederer, Albena}},
  issn         = {{2366-9608}},
  keywords     = {{AF4-SANS; AF4-SAXS; drug delivery system; ellipsoidal nanoparticles; lipid nanoparticles; online/in situ coupling; quinine}},
  language     = {{eng}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Small Methods}},
  title        = {{Structural Profiling of Lipid Nanoparticles at Sub-10 nm Resolution via AF4 Coupled Online to SAXS and SANS}},
  url          = {{http://dx.doi.org/10.1002/smtd.70639}},
  doi          = {{10.1002/smtd.70639}},
  year         = {{2026}},
}