Scalable Synthesis of Self-assembled Magneto-plasmonic Core-Satellite Nanoparticles for Microfluidic Sorting and Bioorthogonal Sensing of Targeted Cells

Multifunctional magneto-plasmonic nanoparticles (MP-NPs) are attracting increasing interest for biomedical applications due to their dual magnetic and optical properties. However, existing synthesis protocols for MP-NPs could be limited by harsh conditions or lengthy, complex procedures. These limitations can hinder the development of nanosystems that work effectively in biological dispersion. In this work, we present a flexible nanoplatform for capture and probe applications, based on MP-NPs and bioorthogonal plasmonic nanoparticles (AuNPs). This system enables efficient cell sorting and surface-enhanced Raman scattering (SERS) detection in complex biological media under dynamic conditions. Magnetic Fe₃O₄ nanoclusters were synthesized using a scalable, aqueous Massart-based protocol. These structures were then densely decorated with electrostatically assembled AuNPs, producing magnetically responsive and plasmonically active nanocomposites with high aqueous stability. A polyethylene glycol (PEG) derivative was used for surface functionalization, improving colloidal stability and enabling broad bio-recognition capability. To enhance detection sensitivity and shift the optical response into the near-infrared (NIR) range, bioorthogonal Raman-active gold nanostars (AuNSts) were integrated into a sandwich configuration with the MP-NPs. The system demonstrated selective sorting and sensitive SERS-based identification of cell subpopulation within a heterogeneous sample. Additionally, the integration of the MP-NPs assay into a 3D-printed microfluidic device allowed controlled nanoparticles manipulation using external magnets, enhancing magnetic separation, hot-spots generation, and assay reusability. Overall, these MP-NPs platform combines scalable synthesis, tunable colloidal and surface properties, and compatibility with microfluidic systems. This work lays the foundation for advanced biosensing approaches in lab-on-chip formats for clinical diagnostics and targeted analysis of rare cell populations.