A novel 3D flexible porous SERS platform for direct plasma-free amino acid profiling and multi-cancer screening

Plasma-free amino acid (PFAA) profiling is crucial for monitoring and evaluating cancer progression. However, there remains a lack of sensitive, simple, and direct methods for rapid PFAA detection. In this study, we developed a vapor-deposited 3D flexible porous structure named FPS Ag - Coated serving as a high-performance surface-enhanced Raman spectroscopy (SERS) platform for ultrasensitive detection of micro PFAAs (10 −4  M). The surface of the platform contains abundant hydroxyl functional groups, which not only confer exceptional flexibility but also significantly minimize background signal interference. The 3D FPS architecture provides densely packed hotspots for Raman signal enhancement while demonstrating excellent cost-effectiveness and scalability for mass production. We systematically evaluated the platform's detection capability using four representative amino acids: fluorescent amino acids (L-tyrosine and L-tryptophan), weakly fluorescent amino acid (L-phenylalanine), and non-fluorescent amino acid (L-serine). Across a concentration range of 10 −1 to 10 −4  M, the platform effectively measured characteristic SERS signals with linear correlation, enabling real-time monitoring and quantitative analysis of PFAAs. When applied to clinical plasma samples from cancer patients, the platform successfully identified PFAAs-specific SERS signal. Subsequent principal component analysis (PCA) achieved discrimination between different cancer types and healthy volunteers with an accuracy exceeding 83.3 %. This work presents a high-performance SERS platform for PFAA recognition, offering a highly adaptable flexible material that could facilitate the clinical translation of SERS-based diagnostics.