High-Tc SQUIDs for biomedical applications: immunoassays, MEG, and ULF-MRI

Doctoral thesis, 2011

This thesis describes high transition temperature superconducting quantum interference devices (high-Tc SQUIDs) for magnetic immunoassays (MIAs), magnetoencephalography (MEG) and ultra-low field magnetic resonance imaging (ULF-MRI). High-Tc dc SQUID sensors were fabricated in single layers of YBa2Cu3O7−δ deposited by pulsed laser deposition and patterned using photolithography on 10×10 mm2 SrTiO3 bicrystal substrates. The best flux noise obtained was 4.6 μΦ0/√Hz and the voltage modulation of the same SQUID was 41 μV at 77 K. Planar first order gradiometers were used for MIA with magnetic nanoparticles (MNPs). The MNPs were multi-core particles containing magnetic single-domain crystals of cobalt-ferrite (CoFe2O4) or magnetite (Fe3O4). Using 2 μl droplets, the detection limit with our system was estimated to be 1.5 ng of MNPs (Fe3O4) with particle diameters of 100 nm. Biomolecule detection using prostate-specific antibodies/antigens was demonstrated. The extrapolated biomolecule sensitivity was 18 ng/ml using a cluster-type assay, and 10 μg/ml was demonstrated using a faster one-step assay. A two-channel MEG system employing high-Tc dc SQUID magnetometers was constructed. The equivalent magnetic field noise of the best SQUID was 25 fT/√Hz above 40 Hz and 43 fT/√Hz at 10 Hz. The lowest 1/f-knee achieved was below 1 Hz, which is an important feature for MEG sensors since most brain activities occur below 100 Hz. With the two-channel system, we successfully recorded the well-known (in standard MEG) α- and the μ-rhythm of human subjects. The α-rhythm was recorded with an amplitude of 800 fT/√Hz in the occipital region of the cortex and was attenuated when the subject had open eyes. The μ-rhythm was recorded in the motor cortex and was attenuated with motor activation. Furthermore, anomalous θ-band activity in the occipital region of the brain was detected which, to our knowledge, has not been reported in the MEG literature. This may indicate the usefulness of high-Tc SQUIDs for MEG where a small distance to the cortex may play a crucial role in detecting new sources. Lastly, an ULF-NMR/MRI system with a high-Tc dc SQUID magnetometer as detector was developed. We obtained the NMR signal from water in a measurement field of 81 μT. The first steps towards imaging were taken by successfully resolving two NMR peaks from two spatially separated water samples in a gradient magnetic field.