Early lung cancer detection based on exosome SPR-Raman biosensors in cord blood samples

In this study, we proposed a novel SPR-Raman biosensing system and utilized it to detect the concentration of umbilical cord blood exosomes for the early detection of cancer. SPR technology detects molecular interactions, analyzing affinity and specificity, while Raman spectroscopy identifies chemical bond characteristics and functional groups in transmembrane proteins and exosome lipid layers. We successfully tested three transmembrane proteins in exosomes and analyzed their interactions, which will aid in the early detection of lung cancer. The experimental results showed that the limits of detection (LODs) of SPR technology for the three transmembrane proteins CD63, CD91, and CD151 were 2.4×10⁵ particles/mL, 1.2×10⁷ particles/mL, and 1.2×10⁷ particles/mL, respectively. Among them, CD63 is a common biomarker of exosomes, while CD91 and CD151 are biomarkers of lung cancer. Therefore, detecting CD91 and CD151 in healthy exosomes requires a higher concentration of exosomes, suggesting that these cancer biomarkers are present at lower levels in healthy exosomes. Raman spectroscopy results revealed distinct peaks for transmembrane proteins, lipids, and nucleic acids in exosomes, confirming successful binding. This further validates the specificity of the SPR response, demonstrating the system's capability to accurately detect exosomal components. This system exhibits high accuracy and sensitivity, serving as a powerful tool for early diagnosis and prognosis. By integrating SPR and Raman spectroscopy, it enhances biomolecular detection, enabling precise analysis of molecular interactions and structural characteristics for improved disease detection and monitoring.