A Printed 3D SERS Array with Hierarchical Micro/Nanostructures Enabled Hotspot Engineering for Ultrasensitive Bio‐Detection

Hotspot engineering of the surface‐enhanced Raman scattering (SERS) system is developed to achieve large enhancement factors, which are limited by small Raman scattering cross‐sections on low‐dimensional structures. Hotspots between the nanogap are difficult to control as discrete occurrences, which are a critical challenge for high‐sensitivity detection. In this work, a hotspot engineering strategy is proposed by introducing 3D hierarchical micro/nanostructures and spatial distribution manipulation. Based on the template‐induced printing strategy, the polystyrene microspheres covered by a quasi‐periodically patterned silver nanoparticles (AgNPs) lattice can be assembled into clusters with precise configurations. The surface curvature of the AgNPs lattice and spatial arrangement of the clusters stimulate electromagnetic wave localization and regulate electromagnetic resonance, creating high‐density and high‐intensity hotspots. Through experiments and theoretical calculations, 3D clusters with a triangular configuration are identified for highly improved Raman response and achieve an ultralow detection limit (LOD) of 10 −20 mol L −1 for R6G, which is the currently lowest detection limit. The 3D platform also detects inflammatory markers of procalcitonin and interleukin‐6 with LODs of 1.84 fg mL −1 and 1.75 pg mL −1 without labels, demonstrating the potential for ultrasensitive bio‐detections. The approach will offer new strategies towards 3D SERS platforms design for simple and ultrasensitive disease diagnosis.