Highly Sensitive Third-Harmonic Detection Method of Magnetic Nanoparticles Using an AC Susceptibility Measurement System for Liquid-Phase Assay

Magnetic sensing techniques have been recently developed to detect biomarkers using magnetic nanoparticles (MNPs) in liquid-phase assays. In the case of alternating current (ac) magnetic susceptibility when detecting a low number of MNPs, the diamagnetic signal of water becomes a major problem at a low signal-to-noise ratio. Therefore, we developed a high-temperature superconducting-quantum-interference-device-based ac susceptibility measurement system that can detect third-harmonic signals from MNPs. On the basis of the nonlinear characteristic of MNPs with large ac magnetic excitation (1.06 kHz), the third-harmonic signal detection (3.18 kHz) of MNPs leads to the elimination of the diamagnetic signal of water. The system consists of excitation and gradiometer pickup coils and a multifunctional circuit device. To improve the signal-to-noise ratio of the third-harmonic measurement, the system has two cancelation functions regarding the fundamental magnetic field. The MNPs are magnetized by using the fundamental magnetic field using the excitation coil. Third-harmonic signals from the MNPs were then detected during the up-and-down movement of the MNPs. We evaluated the detection sensitivity of our system using MNPs. We confirmed that the limit of detection consistency of MNPs was 10 ng by using the third-harmonic measurement method.