In Vivo Dynamic Hotspot-Enhanced Raman Spectroscopy via Reconfigurable Swarming Nanoprobes

Surface-enhanced Raman spectroscopy (SERS) has revolutionized molecular detection through plasmonic signal amplification, yet its translation to living systems remains constrained by two unresolved challenges: rigid substrates lack biological adaptability, while colloidal nanoprobes suffer from unreliable signal reproducibility and poor spatiotemporal control. Herein, we present a bioadaptive SERS platform leveraging magnetically guided swarming nanoprobes to generate dynamic electromagnetic hotspots in vivo. The nanoprobes integrate a magnetic core, plasmonic gold/silver layers, and biocompatible silica coating, enabling precise manipulation and Raman signal enhancement. Programmed magnetic fields drive hierarchical assembly of nanoprobes into chain-like nanostructures with interparticle gap-dependent hotspots, followed by coordinated reconfigurations into dynamically stable swarm geometries. Multiphysics simulations reveal that cyclic nanoprobe assembly-disassembly generates spatially uniform transient hotspots, eliminating the fixed spatial limitations of conventional substrates, while simultaneously inducing convective microflows that actively recruit analytes to enhancement zones. This dual mechanism achieves reproducible amplification with enhancement factors exceeding 2.9×107, over tenfold greater than colloidal systems. Crucially, the swarm’s reconfigurability enables efficient navigation through complex biological topologies, surpassing passive nanoprobes in targeting efficiency. In vivo validation via ultrasound-guided deployment of swarming nanoprobes in rabbit models demonstrates over 10.3-fold Raman signal amplification during intravascular detection, outperforming existing platforms in spatial resolution and operational stability. Our work establishes a new paradigm for in vivo SERS detection by leveraging active matter physics to synergize nanoscale sensing, opening new avenues for real-time molecular diagnostics in living organisms.