In vivo dynamic hotspot-enhanced Raman spectroscopy via reconfigurable swarming nanoprobes

Surface-enhanced Raman spectroscopy (SERS) offers exceptional sensitivity but faces a critical trade-off in living systems: rigid substrates lack biological adaptability, while colloidal nanoprobes suffer from poor signal reproducibility. Herein, we present a bioadaptive SERS platform using magnetically guided swarming nanoprobes. These probes integrate a magnetic core, plasmonic gold/silver layers, and a biocompatible silica coating, enabling programmable assembly under magnetic fields into chain-like nanostructures with interparticle gap-dependent hotspots, followed by coordinated reconfiguration into dynamically stable swarms. Multiphysics simulations reveal that cyclic assembly-disassembly generates transient electromagnetic hotspots while inducing convective flows to actively recruit analytes. This dual mechanism achieves reproducible enhancement factors exceeding 2.9×10⁷, an order of magnitude higher than colloidal systems. In vivo, swarming nanoprobes deployed in rabbit models demonstrate over 10.3-fold Raman signal amplification during intravascular detection. By leveraging active matter physics to synergize nanoscale sensing, this work establishes a new paradigm for in vivo molecular diagnostics.