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Updated: Apr 19, 2026
A Novel Method: Super-selective Adrenal Venous Sampling
Published on: September 15, 2017
High-gradient magnetic separation chip-based small extracellular vesicle isolation for noninvasive subtyping of
Dong Wang1, Jun Zhou2, Zhixin Chen2
1Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Abstract:
Primary aldosteronism (PA), a leading cause of secondary hypertension, remains vastly underdiagnosed due to unreliable screening tools. We developed an integrated platform combining a high-gradient magnetic separation three-dimensional (HGMS-3D) chip and locked nucleic acid (LNA)-enhanced droplet digital polymerase chain reaction (ddPCR) for noninvasive detection of potassium inwardly rectifying channel subfamily J member 5 (KCNJ5) mutations in plasma small extracellular vesicles (sEVs). The HGMS-3D chip uses a nickel mesh-based stereoscopic immunoaffinity capture system, achieving a vesicle isolation efficiency 4.4-fold higher than ultracentrifugation. Coupled with LNA-ddPCR, the platform detects KCNJ5 hotspot mutations [p.Gly151Arg, (G151R); p.Leu168Arg (L168R)] at minor allele frequencies of ≤0.05% (R2 ≥ 0.99), overcoming plasma-derived noise. Clinical validation in 106 patients with PA demonstrated 64.58% sensitivity and 96.88% specificity for sEV-based mutation profiling. The assay identified one aldosterone-producing adenoma (APA) case missed by tissue genotyping, achieving area under the receiver operating characteristic curve (AUC) values of 0.767 ~ 0.852 across mutations. This noninvasive approach could enable curative treatment for millions with undiagnosed PA, advancing precision management of endocrine hypertension through sEV-based liquid biopsy.
