Three-Dimensional SERS Substrates: Architectures, Hot Spot Engineering, and Biosensing Applications.

Three-dimensional (3D) surface-enhanced Raman scattering (SERS) substrates have demonstrated remarkable abilities of ultrasensitive and reproducible molecular detection. The combination of both electromagnetic and chemical enhancement processes, light trapping, and multiple scattering effects of 3D structures are what enhance their performance. The principles of underlying enhancements are summarized systematically, and the main types of 3D substrates-vertically aligned nanowires, dendritic and fractal nanostructures, porous frameworks and aerogels, core-shell and hollow nanospheres, and hierarchical hybrid structures-are categorized in this review. Advances in fabrication techniques, such as template-assisted growth, electrochemical and galvanic deposition, dealloying and freeze-drying, self-assembly, and hybrid integration, are critically evaluated in terms of structural tunability and scalability. Novel developments in the field of biosensing are also highlighted, including non-enzymatic glucose sensing, tumor biomarker sensing, and drug delivery. The remaining limitations, such as low reproducibility, mechanical stability, and substrate standardization, are also noted, and future directions, such as stimuli-responsive designs, multifunctional hybrid platforms, and data-driven optimization strategies of SERS technologies, are also included.