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arXiv · 2605.25465

AI-Driven SERS for Non-invasive and Label-Free Extracellular Vesicle Detection Across Cellular Origins in Tears and Sweat

Yang Li·Xiaoming Lyu·Ling Xia·Kuo Zhan·Haoyu Ji·Lei Qin·Seppo J. Vainio·Jian-An Huang
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Abstract

Wearable sensing technology capable of point-of-care, continuous and non-invasive analysis of exosomes in biofluid such as tears and sweat is an essential part for future personalized medicine. Major detection and identification methods of cell secreted Extracellular Vesicles (EVs) often require labeling and are time-consuming, resulting in low efficiency in EV mechanism research and disease diagnosis. While the label-free Surface-enhanced Raman spectroscopy (SERS) has been combined with deep learning model for EV identification in blood, their application to non-invasive detection of EVs in tears and sweat are missing. Here, we filled this gap by developing an artificial intelligence (AI)-assisted Surface-enhanced Raman spectroscopy (SERS) method based on salt-induced nanoparticle aggregation for fast EV identification in tears and sweat with high accuracy. Significantly, our label-free detection and AI differentiation of EVs from 6 cell lines (HepG2, Hela, 143B, LO-2, BMSC, H8) achieved the identification of EVs in tear fluids from 7 different disease sources with accuracies >92%. Our results showed that this platform can not only distinguish EVs from multiple cell sources but also generate highly reproducible and selective EV signals in tear fluids without a need for chemical labeling or separation steps. Molecular dynamics simulations revealed that silver atoms (Ag) form electrostatic interactions with oxygen atoms of multiple amino acid residues in proteins, suggesting a high affinity. This strategy realizes ultra-sensitive and anti-interference detection of EVs, providing a new idea for the rapid diagnosis of clinical diseases.

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Yang Li, Xiaoming Lyu, Ling Xia, Kuo Zhan, Haoyu Ji, Lei Qin, Seppo J. Vainio, Jian-An Huang. 2026-05-25. AI-Driven SERS for Non-invasive and Label-Free Extracellular Vesicle Detection Across Cellular Origins in Tears and Sweat. https://arxiv.org/abs/2605.25465

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