Ryuzo Kawabata

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.

Note: Low temperature superconductor superconducting quantum interference device system with wide pickup coil for detecting small metallic particles

A one-channel low temperature superconductor superconducting quantum interference device system comprising a second-order axial gradiometer with a sensing area of 10 mm × 190 mm was developed. The gradiometer was mounted in a liquid-helium dewar (450-mm diameter; 975-mm length), with a gap of 12 mm between the pickup coil and the dewar-tail surface. The magnetic field sensitivity was measured to be 16 fT/Hz(1/2) in the white noise regime above 2 Hz. The system was used to measure stainless steel particles of different sizes passing through the sensing area. A 100-μm diameter SUS304 particle was readily detected passing at different positions underneath the large pickup coil by measuring its 1.3-pT magnetic field. Thus, the system was shown to be applicable to quality control of lamination sheet products such as lithium ion batteries.

Immunoassay detection without washing by using AC magnetic susceptibility

Our aim in this study was to demonstrate a stable immunoassay using the decrease of AC magnetic susceptibility without washing to separate bound and unbound magnetic markers. To achieve low noise in the immunoassay system, we examined the arrangement of the MR sensors, the calibration of the distance between the MR sensor and the sample, and the magnetic noise generated from the motor. The immunoassay system was improved based on these factors, and we detected mouse IgG conjugated polymer beads with anti-mouse IgG antibody-coated magnetic markers. The noise that resulted from the vibration of the MR sensor was decreased to about 1/6 by fixing the MR sensor on the excitation coils. The difference in the magnetic signal from each sample was also decreased from 40 % to 6% by calibrating the distance. Magnetic signal with a high signal-to-noise ratio (SN = 10 or more) was obtained by low-speed rotation (8 rpm) of the sample and the narrow band (5.3 Hz) of the lock-in amplifier demodulating the magnetic signal. The decrease of the AC magnetic susceptibility showed a strong correlation with the concentration of mouse IgG. Sensitivity of the immunoassay system could be estimated as about 4 fmol/ml in terms of molecular concentration. Immunoassay detection using AC magnetic susceptibility enabled a highly sensitive immunoassay without the conventional washing process.

Improvement of immunoassay detection system by using alternating current magnetic susceptibility

A major goal with this research was to develop a low-cost and highly sensitive immunoassay detection system by using alternating current (AC) magnetic susceptibility. We fabricated an improved prototype of our previously developed immunoassay detection system and evaluated its performance. The prototype continuously moved sample containers by using a magnetically shielded brushless motor, which passes between two anisotropic magneto resistance (AMR) sensors. These sensors detected the magnetic signal in the direction where each sample container passed them. We used the differential signal obtained from each AMR sensors output to improve the signal-to-noise ratio (SNR) of the magnetic signal measurement. Biotin-conjugated polymer beads with avidin-coated magnetic particles were prepared to examine the calibration curve, which represents the relation between AC magnetic susceptibility change and polymer-bead concentration. For the calibration curve measurement, we, respectively, measured the magnetic signal caused by the magnetic particles by using each AMR sensor installed near the upper or lower part in the lateral position of the passing sample containers. As a result, the SNR of the prototype was 4.5 times better than that of our previous system. Moreover, the data obtained from each AMR sensor installed near the upper part in the lateral position of the passing sample containers exhibited an accurate calibration curve that represented good correlation between AC magnetic susceptibility change and polymer-bead concentration. The conclusion drawn from these findings is that our improved immunoassay detection system will enable a low-cost and highly sensitive immunoassay.

Battery-Powered Wireless Flux-Locked Loop Circuit for Operating High-Tc SQUID

A battery-operated wireless flux-locked-loop (FLL) circuit for operating a high-Tc superconducting quantum interference device (SQUID) was developed and tested. This wireless battery-type FLL circuit consists of an FLL unit and a PC interface. A local area network with the TCP-IP protocol for wireless mode was used for communication between the PC interface and a controlling PC. The battery unit can power the FLL circuits for four hours. The FLL circuit had two bias modes: ac and dc. When the wireless-battery-type FLL circuit was implemented in a SQUID, the system noise generated by a wireless network became intrinsic high-Tc SQUID noise. Also, a 1/f noise was reduced in the case of the ac-bias-current mode. Consequently, the wireless-battery-type FLL circuit can operate a high-Tc SQUID with high sensitivity.