Magnetization Dynamics-Modulated Near-Infrared Mie Scattering Enables Homogeneous Femtomolar Immunosensing for Whole Blood

Abstract Low-abundance biomarkers in whole blood hold immense clinical value for disease diagnosis. However, their detection remains constrained by the difficulty of conventional assays in simultaneously achieving high sensitivity, rapid turnaround, and operational simplicity. Here we introduce optomagnetic particle spectroscopy (OptoMPS), a homogeneous biosensing technology for magnetic label-based immuno-agglutination assays, which overcomes these limitations via the integration of nonlinear magnetization dynamics and orientation-dependent Mie scattering of magnetic particles. Under an optimally biased oscillating magnetic field, numerical simulations indicate that third-harmonic optical modulation can be markedly amplified by the combined effects of hydrodynamic size expansion, effective magnetic moment reduction, and Mie scattering, yielding substantial signal contrast between agglutinated and monomeric magnetic particles under idealized monomer–dimer conditions. Using near-infrared excitation and magnetic actuation to suppress biological matrix background, the platform achieves a detection limit of 63 fM (1.54 pg/mL) for cardiac troponin I (cTnI) in 10% (v/v) routine whole blood within 5 min. Sample pretreatment is required only for severely lipemic specimens. Preliminary method comparison using 58 clinical samples shows good agreement with the commercial chemiluminescence immunoassay used in routine clinical practice, with good capacity to distinguish cTnI-positive and cTnI-negative samples classified by the reference method. These results demonstrate that OptoMPS is an effective platform for femtomolar biomarker detection in complex biological matrices.