Rapid Detection and Purification of Extracellular Vesicles for Hepatocellular Carcinoma Screening Using a Plasmonic Metasurface Integrated with the Kolmogorov-Arnold Network

ACS Nano. 2025 Dec 16;19(49):41557-41570. doi: 10.1021/acsnano.5c11740. Epub 2025 Dec 4.

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of global cancer-related mortality, with delayed diagnosis adversely affecting patient outcomes. Liquid biopsy techniques using small extracellular vesicles (EVs) offer potential for cancer detection, though current methods are often time-consuming and require complex equipment, limiting clinical utility. Here, we report a metasurface-enhanced EV detection chip (metaEVchip) platform for the dynamic monitoring of HCC-specific EVs, enabling rapid detection and purification. This system provides results within 5 min. The platform integrates a plasmonic metasurface with a Kolmogorov-Arnold network (KAN) to facilitate real-time EV capture, enhancing detection speed while achieving an area under the curve (AUC) of 0.914 for HCC screening. By optimizing the purification process and incorporating complementary detection of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKAII), the AUC for HCC screening reaches 0.961 in an external validation set. These results effectively differentiate HCC from benign liver diseases (BLD) and early-stage HCC from cirrhosis, addressing limitations of conventional EV detection and demonstrating the potential for rapid cancer screening.

Keywords: cancer screening; deep learning; extracellular vesicles; plasmonic metasurface; rapid detection.

MeSH terms

  • Biomarkers
  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / pathology
  • Early Detection of Cancer* / methods
  • Extracellular Vesicles* / chemistry
  • Extracellular Vesicles* / metabolism
  • Humans
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / pathology
  • Protein Precursors
  • Prothrombin
  • alpha-Fetoproteins / analysis

Substances

  • alpha-Fetoproteins
  • acarboxyprothrombin
  • Protein Precursors
  • Prothrombin
  • Biomarkers