Electrochemical immunosensor-enabled liquid biopsy of extracellular vesicles for diagnosis of metabolic dysfunction-associated steatohepatitis
Nguyen, T. T. Q.; Choi, D.; Lee, S.; de Hoyos-Vega, J. M.; Daniel, P. V.; Mauer, A. S.; Eller, M. J.; Giron, A.; Cedillo-Alcantar, D. F.; Stybayeva, G.; Graham, R.; Allen, A.; Lazaridis, K.; Malhi, H.; Revzin, A.
Show abstract
Accurate, noninvasive biomarkers for diagnosis and longitudinal monitoring of metabolic dysfunction-associated steatohepatitis (MASH) remain an urgent unmet clinical need. Here, we describe an electrochemical immunoassay that involves capturing hepatic extracellular vesicles (EVs) on antibody-modified electrodes followed by detecting EV-borne biomarkers using redox active gold nanoparticles (AuNPs). The intensity of electrochemical redox signal represents a quantitative measure of biomarker abundance. Three MASH-associated biomarkers-S100A11, TNF-, and TGF-{beta}1 were analyzed on hepatic EVs to assess steatotic, inflammatory, and fibrotic states of the diseased liver. The electrochemical signals for individual biomarkers were added into a composite EVMASH score. Plasma samples from 28 patients with MASH, 22 healthy controls, and 27 patients with non-MASH liver disease were scored in this manner, revealing 100% accuracy in the training cohort and >90% accuracy in an independent validation cohort. Our electrochemical immunosensor represents a minimally invasive liquid liver biopsy, offering a promising alternative to solid liver biopsies for screening and monitoring of MASH.
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