Multi-shelled nano-spheres in biosensing: classification, synthesis and applications

Abstract Multi-shelled hollow nanomaterials with diverse compositions and architectures have garnered significant attention due to their unique structural advantages, including high surface-to-volume ratios, tunable inner cavities, and enhanced physicochemical properties. While single-shelled hollow structures have been extensively explored, multi-shelled architectures offer superior functionality, making them promising candidates for advanced applications. This review provides a comprehensive overview of recent advancements in the synthesis, classification, and biosensing applications of multi-shelled spherical nanomaterials. Various synthesis approaches, including hard templating, soft templating, sacrificial templating, and template-free methods, are critically analyzed with a focus on their advantages, limitations, and challenges. The potential of multi-shelled nanoparticles in biosensing is explored, particularly in electrode-based detection and surface-enhanced Raman scattering (SERS) techniques, enabling rapid, sensitive, and selective identification of harmful organisms, viruses, and contaminants. Furthermore, this review emphasizes the importance of developing greener, scalable, and cost-effective synthetic strategies to meet the growing demand for real-world applications. Future research directions are highlighted, including the integration of multi-shelled nanospheres into point-of-care diagnostic platforms, the design of multifunctional nanocomposites, and the enhancement of biosensing performance through novel hybrid materials. These advancements are expected to pave the way for next-generation biosensors capable of real-time, in vivo , and multiplexed detection, contributing significantly to healthcare, environmental monitoring, and food safety.