A PLA-mediated transistor biosensor enables specific identification of tumor-derived exosomal PD-L1

The expression of programmed death ligand 1 (PD-L1) on tumor-derived exosomes (tExos) forecasts the efficacy of immunotherapy and tumor diagnosis. Due to the heterogeneity of exosomes, current detection methods face challenges in distinguishing between tumor-derived and non-tumor-derived exosome PD-L1. To address this challenge, we introduce a novel field effect transistor (FET) biosensor based on proximity ligation assay (PLA) technology. This approach uses a single probe to simultaneously recognize two biomarkers on exosomes to identify tumor-derived exosome PD-L1 (tExo_-PD-L1). This method, for the first time, integrates the PLA strategy with FET technology, allowing for tracking of exosomes that co-express multiple biomarkers. In clinical diagnostics, this strategy not only significantly improves the sensitivity and specificity, but also enhances the precision and accuracy, compared to conventional approaches that identify total Exo_-PD-L1 or Exo_-EpCAM using a single biomarker. This technology holds promise for enhancing the reliability of using exosomes as biomarkers in clinical diagnostics and further exploring the biological functions of exosomes more effectively.