Shu-Hsien Liao

High-Tc SQUID gradiometer system for magnetocardiography in an unshielded environment

We have designed a magnetocardiography (MCG) system that is capable of measuring magnetocardiograms in an unshielded environment. In order to carry out such a measurement, one has to contend with various ambient noise sources. These include power line and RF interference, microphonics pickup, fluctuations in the earth’s magnetic field, and electrostatic pickup. Earlier solutions devised to overcome these problems have entailed the use of a second-order gradiometer inside a deep mine or inside a magnetically shielded enclosure [1]. Apart from the above problems which are common to both low-Tc and high-Tc SQUIDs, high-Tc SQUIDs exhibit additional 1/f noise [2]. This noise is the result of hopping of flux vortices that are trapped in the body of the field cooled high-Tc SQUID, and can only be eliminated by zero-field cooling the SQUID.

Clinic Applications in Assaying Ultra-Low-Concentration Bio-Markers Using HTS SQUID-Based AC Magnetosusceptometer

The HTS superconducting quantum interference devices (SQUID) magnetometers meets the requirement for the early-stage or hard-to-detect in-vitro diagnosis because of its ultrahigh sensitivity. For example, the demand for assaying the ultra-low-concentration biomarkers of tumors is always existing. It would be better to quantitatively detect the vascular endothelial growth factor (VEGF) at the concentration of 1 pg/ml for diagnosing the early-stage malignancy. In this work, by using the HTS SQUID-based ac magnetosusceptometer and biofunctionalized magnetic nanoparticles, the low-detection limit for VEGF is sub-pg/ml. Furthermore, the clear difference in the VEGF concentrations in sera was found between normal people and tumor patients. Another example to demonstrate the high sensitivity and high specificity of the immunoassay based on the HTS SQUID ac magnetosusceptometer is the detection of biomarkers for Alzheimers Disease. The biomarkers for Alzheimers Disease in plasma are very rare (around 1-100 pg/ml). It is hardly possible to assay the biomarkers in plasma. Here, it has been demonstrated that the HTS SQUID ac magnetosusceptometer can detect the biomarkers at very low concentrations ( ~ 1 pg/ml). Through the assays on the biomarkers in plasma of more than 100 people, the clinical accuracy is almost 90%. These results show the niches of clinical applications using the HTS SQUID ac magnetosusceptometer.

Use of a high-Tc SQUID-based nuclear magnetic resonance spectrometer in magnetically unshielded environments to discriminate tumors in rats, by characterizing the longitudinal relaxation rate

This study uses a sensitive, high-Tc SQUID-detected nuclear magnetic resonance spectrometer in magnetically unshielded environments to discriminate liver tumors in rats, by characterizing the longitudinal relaxation rate, T1−1. The high-Tc SQUID-based spectrometer has a spectral line width of 0.9Hz in low magnetic fields. It was found that relaxation rate for tumor tissues is (3.6 ± 0.02) s−1 and the relaxation rate for normal tissues is (7.7 ± 0.02) s−1. The difference in the longitudinal relaxation rates suggests that water structures around the DNA of cancer cells are different from those of normal tissues. The optimized detection sensitivity for the established system is 0.21 g at the present stage. It is concluded that T1−1 can be used to distinguish cancerous tissues from normal tissues. The high-Tc, SQUID-detected NMR and MRI in magnetically unshielded environments may also be useful for discriminating other tumors.

Eight-Channel AC Magnetosusceptometer of Magnetic Nanoparticles for High-Throughput and Ultra-High-Sensitivity Immunoassay

An alternating-current magnetosusceptometer of antibody-functionalized magnetic nanoparticles (MNPs) was developed for immunomagnetic reduction (IMR). A high-sensitivity, high-critical-temperature superconducting quantum interference device was used in the magnetosusceptometer. Minute levels of biomarkers of early-stage neurodegeneration diseases were detectable in serum, but measuring each biomarker required approximately 4 h. Hence, an eight-channel platform was developed in this study to fit minimal screening requirements for Alzheimer’s disease. Two consistent results were measured for three biomarkers, namely Aβ40, Aβ42, and tau protein, per human specimen. This paper presents the instrument configuration as well as critical characteristics, such as the low noise level variations among channels, a high signal-to-noise ratio, and the coefficient of variation for the biomarkers’ IMR values. The instrument’s ultrahigh sensitivity levels for the three biomarkers and the substantially shorter total measurement time in comparison with the previous single- and four-channels platforms were also demonstrated in this study. Thus, the eight-channel instrument may serve as a powerful tool for clinical high-throughput screening of Alzheimer’s disease.

Magnetic Tools for Medical Diagnosis

Magnetic tools here are defined as the nanotechnologies for medical diagnosis, including in vitro diagnostics, ex vivo examination, and in vivo imaging by using magnetic nanoparticles (MNPs). In this chapter, we describe the mechanism, instrumentation, and medical results of different advanced magnetic tools.

Magnetic particle imaging with multichannel coil arrays

Magnetic particle imaging was introduced to an noninvasive method for 3-dimensional imaging tool for tracing the distribution of magnetic particle in vivo. However the proposed method should not only applying a high strength AC magnetic field to induce the third harmonic magnetic signal form the nonlinear magnetized magnetic nanoparticles but also applying three strong gradient fields and three strong magnetic fields to construct a small field-free point (FFP) and scan the FFP for imaging. The strength of gradient field should be several T/m for a high spatial resolution about several mm. It limits the imaging size and the cost of high power supplies for strong scanning magnetic fields is expensive. Here, we propose a new magnetic particle imaging method by using pickup coil array and a strong ac exciting field instead of the gradient fields and scanning field. This method reaches the real time imaging and low cost and promise for the industrialization in the new future.

Magnetic particle imaging with use of second harmonic response of magnetization

Magnetic particle imaging (MPI), as introduced by Gleich and Weizenecker, is based on utilizing the nonlinear magnetization response M for detection of superparamagnetic iron oxide nanoparticles (MNP). The excited M contains not only the fundamental excitation frequency ω0 but also its harmonics when applying an ac excitation magnetic field. To improve the detection sensitivity for the magnetization M of MNP and the imaging technique based on the detection of a second harmonic response, a 2D imaging system consisting of four magnetic fields, dc bias field Hdc, ac modulation field Hac, gradient field of Z-axis and gradient field of X-axis have been constructed. The advantage of the detection of a second harmonic response is that no large ac modulation field Hac is required. This study demonstrated a MNP detection method using a second harmonic of magnetic response. The position of the 10-microlitre MNP sample was clearly indicated in 2D imaging.

Spin-Spin and Spin-Lattice Relaxation of Protons in Ferrofluids Characterized With a High-

In this work, the relaxation rates of ferrofluids are characterized using a high-Tc SQUID-based nuclear magnetic resonance spectrometer in different field strengths and temperatures. It was found that the longitudinal relaxation rate, 1/T1, of ferrofluids measured in a high field strength is significantly higher than that measured in a low field strength. We attribute this to the magnetic-field gradients from the magnetization of magnetic nanoparticles that accelerate the T1-relaxation more in a high strength of magnetic fields than they are in a low strength of magnetic fields. Furthermore, T1 and T2 decrease when temperature increases, where T2 is the transverse relaxation time. This is due to the improved field-homogeneity seen by protons spins at high temperatures, attributed to the enhanced Brownian motion of magnetic nanoparticles. Characterizing the relaxation rates will be helpful for further use of ferrofluids as contrast agents in low-field MR imagings.