Authors
Zhiheng Luo, Pengbo Zhang, Mou Li, Xuejian Cui, Zixuan Liu, Baoshui Zhang, Hao Wang, Fangfang Wang, Tian Qiu, Zhengping Li
Published in
Biosensors & bioelectronics. Volume 314. Pages 119196. Sep 04, 2026. Epub Sep 04, 2026.
Abstract
Tumor-derived exosomes (TEXs) hold immense promise as biomarkers for cancer diagnosis, but sensitive and accurate identification is hindered by their intrinsic heterogeneity and extreme scarcity. Co-profiling of exosomal protein and microRNA (miRNA) at the single-molecule level may greatly enhance the precision of cancer diagnosis and prognosis. Herein, we present a single microbead-confined dual-mode detection system that selectively captures TEXs for concurrent quantification of protein and miRNA biomarkers. Exosomal proteins are quantified by measuring fluorescence signal concentrated on a single microbead-based enrichment platform. After on-bead lysis, individual miRNA is recognized by the two peptide nucleic acids (PNAs) to form a strict one-to-one correspondence with the intense light-scattering signal of gold nanoparticles (AuNPs), enabling single-molecule counting analysis. Through comprehensive profiling, a panel of four conjoint biomarkers achieve the highest diagnostic accuracy of 98.33%, outperforming any individual markers or alternative combinations. Importantly, this is the first demonstration of a universal PNA modification strategy that harnesses a DNA mediator to prevent AuNPs self-aggregation. This platform can also be adapted to other cancers by simply changing the aptamers and PNAs to target corresponding biomarkers, showing significant potential for advancing exosome-based liquid biopsies and accelerating the development of next-generation clinical diagnostic tools.
PMID:
42702176
Bibliographic data and abstract were imported from PubMed on 07 Sep 2026.
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