Abstract
Lung cancer with heterogeneity has a high mortality rate due to its late-stage detection and chemotherapy resistance. Liquid biopsy that discriminates tumor-related biomarkers in body fluids has emerged as an attractive technique for early-stage and accurate diagnosis. Exosomes, carrying membrane and cytosolic information from original tumor cells, impart themselves endogeneity and heterogeneity, which offer extensive and unique advantages in the field of liquid biopsy for cancer differential diagnosis. Herein, we demonstrate a Gramian angular summation field and MobileNet V2 (GASF-MobileNet)-assisted surface-enhanced Raman spectroscopy (SERS) technique for analyzing exosomes, aimed at precise diagnosis of lung cancer. Specifically, a composite substrate was synthesized for SERS detection of exosomes based on Ti(3)C(2)Tx Mxene and the array of gold-silver core-shell nanocubes (MGS), that combines sensitivity and signal stability. The employment of MXene facilitates the non-selective capture and enrichment of exosomes. To overcome the issue of potentially overlooking spatial features in spectral data analysis, 1-D spectra were first transformed into 2-D images through GASF. By using transformed images as the input data, a deep learning model based on the MobileNet V2 framework extracted spectral features from higher dimensions, which identified different non-small cell lung cancer (NSCLC) cell lines with an overall accuracy of 95.23%. Moreover, the area under the curve (AUC) for each category exceeded 0.95, demonstrating the great potential of integrating label-free SERS with deep learning for precise lung cancer differential diagnosis. This approach allows routine cancer management, and meanwhile, its non-specific analysis of SERS signatures is anticipated to be expanded to other cancers.