In this paper, we propose improved methods of liquid-phase detection of biological targets utilizing magnetic markers and a high-critical-temperature superconducting quantum interference device (SQUID). For liquid-phase detection, the bound and unbound (free) markers are magnetically distinguished by using Brownian relaxation of free markers. Although a signal from the free markers is zero in an ideal case, it exists in a real sample on account of the aggregation and precipitation of free markers. This signal is called a blank signal, and it degrades the sensitivity of target detection. To solve this problem, we propose improved detection methods. First, we introduce a reaction field, Bre, during the binding reaction between the markers and targets. We additionally introduce a dispersion process after magnetization of the bound markers. Using these methods, we can obtain a strong signal from the bound markers without increasing the aggregation of the free markers. Next, we introduce a field-reversal method in the measurement procedure to differentiate the signal from the markers in suspension from that of the precipitated markers. Using this procedure, we can eliminate the signal from the precipitated markers. Then, we detect biotin molecules by using these methods. In an experiment, the biotins were immobilized on the surfaces of large polymer beads with diameters of 3.3 µm. They were detected with streptavidin-conjugated magnetic markers. The minimum detectable molecular number concentration was 1.8×10-19 mol/ml, which indicates the high sensitivity of the proposed method.

Magnetospinography (MSG) is one of the most promising techniques to detect the nerve activity of spinal cords thanks to its noninvasiveness and high spatial/temporal resolutions. Multichannel superconducting quantum interference device (SQUID) MSG measurement systems optimized for supine subjects have been developed previously and employed in clinical applications in hospitals. Magnetic source analyses of MSG data based on spatial filter techniques reveal the transition of reconstructed current distributions adjacent to the spinal cord. The propagation of the neural signals was noninvasively visualized. The MSG measurements provide significant diagnostic information such as irregularities in the transitions of the reconstructed current distribution and/or considerable decreases in the current intensity at the lesion. Such functional imaging of the spinal cord in addition to conventional neurologic examinations and morphological imaging will be fairly effective in presurgical lesion localizations of the spinal cord.

The superconducting quantum interference device (SQUID) is a transducer that converts magnetic flux into voltage. Its range of linear conversion, however, is very restricted. To overcome its narrow dynamic range, a flux-locked loop (FLL) is used to feedback the output field to cancel the input field. This prevents the operating point of the SQUID from moving far away from the null point. In this paper, an emulator for the SQUID sensor and the feedback coil has been proposed. Magnetic coupling between the original field and the generated field by the feedback coil was emulated by electronic circuits. By using the emulator, FLL circuits can be analyzed and optimized without use of SQUID sensors. This is a useful feature, especially in the early stage of development of the MCG system when a magnetically shielded room or real SQUID sensors may not yet be available. The emulator may also be used as a test signal generator for multi-channel gain calibration and for system maintenance.

This study shows the results of evaluating the flux noises at low frequency when the alternating current(AC) bias direct offset integrated technique(DOIT) with additional positive feedback (APF) is used in a high-Tc dc superconducting quantum interference device (SQUID). The AC-bias DOIT can reduce low-frequency noise without increasing the level of white noise because each operating point in the two voltage-flux characteristics with AC bias can always be optimum on the magnetometer in the high-Tc dc-SQUID. APF can improve the effective flux-to-voltage transfer function so that it can reduce the equivalent flux noise due to the voltage noise of the preamplifier in the magnetometer. The use of APF combined with the AC-bias DOIT reduced the noise of the magnetometer by factors of 1.5 (33µΦ0/Hz vs. 50 µΦ0/Hz) at100 Hz, 3.5 (43 µΦ0/Hz vs. 150 µΦ0/Hz) at 10 Hz, and 5.2 (67 µΦ0/Hz vs. 351 µΦ0/Hz) at 1 Hz as compared with the noise levels that were obtained with the static-current-bias DOIT. The contribution of the factors at 1 Hz is about 2 by APF and 2.6 by AC bias. The performance of improving the flux noise in the AC -bias DOIT with APF is almost equal to that of the flux locked loop (FLL) circuits in which the flux modulation uses a coupling system with a transformer and with the AC bias.