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<p>Diagnosing intracerebral hemorrhage (ICH) in prehospital settings remains challenging due to unavailability of immediate neuroimaging, clinical overlap with ischemic stroke, and absence of validated circulating biomarkers for time-critical settings. Extracellular vesicles (EVs), subcellular structures capable of transporting biomolecular payloads (e.g., proteins, nucleic acids) across the blood-brain barrier, have emerged as compelling diagnostic candidates for ICH. Nevertheless, their clinical translation has been impeded by inherent biophysical heterogeneity, particularly polydisperse size distributions. To address this limitation, we engineer a <b>s</b>teric <b>h</b>indrance-mediated <b>E</b>V <b>a</b>nalysis and size <b>f</b>ractionation (SHEAF) platform, integrating steric hindrance-based size fractionation with membrane protein profiling to stratify EVs into three size subtypes within a 45-min workflow. Systematic evaluation using the SHEAF platform reveals that the 90 − 180 nm EV subtype exhibits superior discriminative capacity in differentiating ICH from ischemic stroke plasma specimens. This technology not only advances rapid prehospital ICH diagnostics but also establishes a method for elucidating size-dependent EV functionalities across neurological pathologies.</p>

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Steric hindrance-mediated extracellular vesicle size fractionation for rapid prehospital diagnosis of intracerebral hemorrhage

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月9日

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  • Xingjie Wu,
  • Shasha Xiong,
  • Litao Zhang,
  • Yueyue Zhao,
  • Zhilu Sun,
  • Likun Wang,
  • Weifeng Long,
  • Qianqian Guo,
  • Yu-E Wang,
  • Ying Chen,
  • Ling Tao,
  • Wei Li,
  • Xiangchun Shen,
  • Guofeng Wu,
  • Haitao Zhao

摘要

Diagnosing intracerebral hemorrhage (ICH) in prehospital settings remains challenging due to unavailability of immediate neuroimaging, clinical overlap with ischemic stroke, and absence of validated circulating biomarkers for time-critical settings. Extracellular vesicles (EVs), subcellular structures capable of transporting biomolecular payloads (e.g., proteins, nucleic acids) across the blood-brain barrier, have emerged as compelling diagnostic candidates for ICH. Nevertheless, their clinical translation has been impeded by inherent biophysical heterogeneity, particularly polydisperse size distributions. To address this limitation, we engineer a steric hindrance-mediated EV analysis and size fractionation (SHEAF) platform, integrating steric hindrance-based size fractionation with membrane protein profiling to stratify EVs into three size subtypes within a 45-min workflow. Systematic evaluation using the SHEAF platform reveals that the 90 − 180 nm EV subtype exhibits superior discriminative capacity in differentiating ICH from ischemic stroke plasma specimens. This technology not only advances rapid prehospital ICH diagnostics but also establishes a method for elucidating size-dependent EV functionalities across neurological pathologies.