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. Magnetically controlled swarms of bioadaptive SERS nanoprobes dynamically reconfigure to generate transient electromagnetic hotspots and recruit analytes via convective flows, achieving over tenfold Raman signal amplification for in vivo detection.