A magnetic immunoassay (MIA) has attracted attention of a lot of researchers since it is expected to realize a rapid and high-sensitive medical diagnosis. The MIA utilizes magnetic nanoparticles (MNPs), which generally show superparamagnetic properties, functionalized with antibodies to react with specific antigens. When the MNPs are conjugated with antigens in solutions, an AC magnetic susceptibility of MNPs decreases due to an increment in the particle volume. Thus, the concentration of the antigens could be measured by measuring the magnetic signals from the MNPs. Recently, a magnetic immunoassay system using high-T_c SQUIDs has been developed [1]. This system measures the third harmonic of the magnetic signals from the MNPs by applying the AC magnetic field with the frequency of 1.06 kHz and the amplitude of 8.5 mT_p-p. A first-order differential coil was mounted coaxially with an excitation coil to detect the signals. The detected signals were transferred to the planar superconductive coils magnetically coupled with an HTS-SQUID chip after being amplified by a lock-in circuit. We used ramp-edge junctions made from SmBa₂Cu₃O_y (SmBCO) and La_0.1-Er_1.95Cu₃O_y (La-ErBCO) for the HTS-SQUID. The sample solution in a quartz tube was located along the center axis of the coils.

However, the AC magnetic susceptivity of MNPs also decreases by aggregation of the MNPs, and it is difficult to distinguish the reduction of the signals by the conjugation from the signals by the aggregation. Therefore, quantitative measurement of the MIAs was challenging.

In our group, nonthermally dispersion of MNPs, driven by irradiating aggregated MNPs with femtosecond laser pulses [2], has been proposed. In this study, to introduce femtosecond laser pulses to the MIA system, a multimode optical fiber cable was installed along the central axis of the coils. Thus, measurement of the magnetic signals during the laser pulse irradiation could be realized.

The multimode fiber with a core diameter of 105 μm was used, which was connected to the femtosecond laser, which produced the laser pulses with a pulse width of 150 fs at FWHM, the center wavelength of 780 nm, and the repetition rate was 70 MHz, respectively.

Figure 1 shows the time evolution of the magnetic signal intensity of MNPs during the femtosecond laser irradiation. The diameter of MNPs was 180 nm in average. The concentration of sample particles was 2 mg/ml in 50 μl. The MNPs were firstly sonicated, and after leaving the sample for 35 min., we started laser irradiation (the start time was indicated as 3 min in Fig.1.). The signal intensities plotted in Fig.1 were normalized at the time is zero. The magnetic signal intensity increased by the laser irradiation due to the dispersion of the magnetic particles. The change in the signal intensity was proportionally increased by increasing the average power of the femtosecond laser pulses. The ratio of the signal at 45 min to 0 min were respectively 5.3%, 15.7%, and 31.8% for 5 mW, 10mW, and 25 mW. This result indicates that the dispersion of MNPs by the femtosecond laser during the measurements was realized.

[1] Mizoguchi et al., IEEE Trans.Appl.Supercond,Vol.26,No.5,August 2016
[2] K. Kishimoto et al., Presented at the 34^th International Symposium on Superconductivity (ISS 2021), 30 Nov– 2 Dec, On-line, ED2-3

Fig.1 Laser output dependence of signal recovery

Keywords: Magnetic nano particles, SQUID, Magnetic immunoassay