Field-Swept Magnetic Particle Spectroscopy: A Single-Harmonic Method for Simultaneous Determination of Magnetic Nanoparticle Types and Quantities

Abstract

Magnetic particle spectroscopy (MPS) allows for highly sensitive and real time characterization of magnetic nanoparticles (MNPs). When combined with surface-modified MNPs that can specifically bind to biomarkers, MPS can serve as a quantitative biosensing platform and have shown enormous potential in point-of-care diagnosis. To improve diagnostic efficiency and accuracy, the simultaneous detection of multiple biomarkers has been studied in MPS, which requires the simultaneous determination of the type and quantity of MNPs. Current methods generally rely on the higher order harmonics (e.g., third to fifth harmonic ratio) of the MNPs’ magnetic responses to the excitation fields, but facing challenges at low concentrations or with small-sized MNPs that are difficult to generate sufficient harmonics. In this paper, we propose a single-harmonic method for simultaneous determination of MNP types and quantities, named field-swept magnetic particle spectroscopy (FS-MPS). An adjustable static magnetic field perpendicular to the alternating magnetic field is introduced and MNPs’ field-dependent response is registered from the static field direction. By comparing simulation results of serval system configurations and the field-swept spectra of different harmonics, we found that the second harmonic component of the MNP signal combines good specificity and robustness with no direct feed-through interference issues. We built the first FS-MPS device and carried out experiments of binary MNP mixtures to verify the effectiveness of the proposed method. Our experimental results showed that the proposed method has up to 90% accuracy for the simultaneous determination of two types of MNPs with a maximum concentration ratio of 9:1. The proposed method can in principle determine more types of MNPs simultaneously, providing an effective tool for the detection of multiple biomolecular markers.