Comparative Evaluation of Relaxation-Based Bio-Sensing Performance of Magnetic Nanoparticles Using Magnetic Particle Spectroscopy

Abstract

Magnetic Particle Spectroscopy (MPS) is a highly sensitive, label-free technique for detecting biomolecular interactions through the nonlinear magnetization of magnetic nanoparticles (MNPs). This study presents a comparative performance evaluation of four commercial carboxyl-functionalized MNPs as: Synomag®, Perimag®, Resovist®, and SHP-30 (Ocean NanoTech), to assess their biosensing suitability using MPS. Measurements at 5, 15, and 25 kHz in water, glycerol, and agarose characterized medium- and frequency-dependent relaxation: SHP-30 exhibited predominantly Brownian relaxation with the highest sensitivity to hydrodynamic size changes; Perimag showed slower Brownian behavior with reduced sensitivity; Resovist was predominantly Néel-dominated; and Synomag displayed mixed relaxation. For biosensing efficiency, all four MNPs were conjugated with H1N1 hemagglutinin protein via EDC–NHS chemistry, and bio-conjugation was confirmed by FT-IR (amide I/II) and DLS (increased hydrodynamic size). ICP-MS quantified the retained iron content after conjugation and washing, and all samples were normalized to the same iron mass for MPS measurement. Frequency-tuned MPS measurements identified that SHP-30 exhibited significantly greater signal suppression at low frequencies (~7.74 kHz) upon protein binding, enabling protein detection limit down to 10 nM. Collectively, these findings establish SHP-30 as a highly sensitive and efficient candidate for biomarker-conjugated MPS diagnostics, with potential utility in infectious disease detection and point-of-care applications.