Ratiometric electrochemical OR gate assay for NSCLC-derived exosomes

Non-small cell lung cancer (NSCLC) is the most common pathological type of LC and ranks as the leading cause of cancer deaths. Circulating exosomes have emerged as a valuable biomarker for the diagnosis of NSCLC, while the performance of current electrochemical assays for exosome detection is constrained by unsatisfactory sensitivity and specificity. Here we integrated a ratiometric biosensor with an OR logic gate to form an assay for surface protein profiling of exosomes from clinical serum samples. By using the specific aptamers for recognition of clinically validated biomarkers (EpCAM and CEA), the assay enabled ultrasensitive detection of trace levels of NSCLC-derived exosomes in complex serum samples (15.1 particles mu L-1 within a linear range of 10(2)-10(8) particles mu L-1). The assay outperformed the analysis of six serum biomarkers for the accurate diagnosis, staging, and prognosis of NSCLC, displaying a diagnostic sensitivity of 93.3% even at an early stage (Stage I). The assay provides an advanced tool for exosome quantification and facilitates exosome-based liquid biopsies for cancer management in clinics.

Automated summary

Non-small cell lung cancer(NSCLC) is the most common type of lung cancer and the main cause of cancer death, while circulating exosomes have been identified as a valuable biomarker for NSCLC diagnosis. In this study, a ratiometric biosensor integrated with an OR logic gate was developed for surface protein profiling of NSCLC-derived exosomes in clinical serum samples. The assay showed ultrasensitive detection of trace levels of NSCLC-derived exosomes in complex serum samples, outperforming the analysis of six serum biomarkers for accurate NSCLC diagnosis, staging, and prognosis, even at an early stage with a diagnostic sensitivity of 93.3%. This assay provides an advanced tool for exosome quantification and facilitates exosome-based liquid biopsies for cancer management in clinics.