Precise Genotyping Via Surface‐Enhanced Raman Spectroscopy‐Based Optical Sensing Chip for Guiding Targeted Therapy in Lung Cancer

Abstract The emergence of “precision medicine” marks a notable shift in cancer treatment, moving from a tumor type–oriented approach to a more targeted, gene‐oriented approach. Detecting low‐abundance mutant genes in blood is challenging but crucial for personalized treatment plans. Herein, a novel platform combining catalytic hairpin self‐assembly (CHA)‐mediated self‐calibrating surface‐enhanced Raman spectroscopy (SERS) with a high‐throughput Raman system (CCSPS) was designed. This platform enables ultrasensitive and rapid genotype analysis of gene mutations. The development of CCSPS specifically targets EGFR mutations, which serve as crucial therapeutic targets for precision therapy in lung cancer. This system shows excellent sensitivity and selectivity, capable of detecting multiple EGFR mutations (Del‐19, L858R, and T790M) with a detection limit as low as attomolar levels. Additionally, precise genotyping analysis was successfully conducted on 42 clinical samples using the CCSPS, yielding results consistent with those obtained through next‐generation sequencing. These results underscore the efficacy of the CCSPS in noninvasively identifying circulating tumor DNA (ctDNA) mutations, facilitating immediate therapeutic decision making at the bedside. In summary, the CCSPS is a fast, accurate, versatile, and compact testing system capable of precisely screening individuals who stand to benefit from targeted therapy, thus promoting personalized and precise healthcare.