Chemiluminescent optical fiber biosensing platform with tyramide signal amplification for ultrasensitive detection of tumor-derived exosomes

Exosomes have emerged as promising non-invasive biomarkers in liquid biopsy for the early diagnosis and treatment of cancers. Traditional methods for exosome analysis are often limited by complex procedures and costly instruments, as well as challenges including low signal differentiation and interference from large amounts of free proteins in body fluids. Herein, we propose a novel biosensing platform that integrates tyramide signal amplification (TSA) with a lipid-anchored chemiluminescent optical fiber sensor (COFS). The platform utilizes distearoyl phosphatylethanolamine-polyethylene glycol (DSPE-PEG) as lipid-anchor to capture exosomes and horseradish peroxidase (HRP)-labeled aptamers for specific recognition. The dual identification of surface proteins and membrane structure avoids interference from free proteins. The TSA-based signal amplification system significantly enhances detection sensitivity, benefiting from the abundance of proteins in exosomal membranes that function as deposition sites for active tyramine. The proposed TSA-COFS platform offers a cost-effective solution to the challenges of exosome quantitation, enabling rapid analysis, ultrasensitive detection and point-of-care profiling of tumor-derived exosomes within biological samples. The efficacy of the platform was demonstrated by analyzing Mucin 1 protein (MUC1)-expressing exosomes from human clinical serum samples. The results show that the method can achieve rapid and accurate determination of exosomes with high selectivity and an extremely low limit-of-detection of 6.76 particles/μL. A home-made portable device, equipped with the sensor probe, a "plug-in" operation of the reagent strip, a battery-powered photon counter and a touch-screen computer, is used for the assays, demonstrating the potential practical value of the TSA-COFS for exosome quantitation and point-of-care testing (POCT) applications.