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An array of highly sensitive biomagnetic sensors of the superconducting quantum interference detector (SQUID) type can identify disease in vivo by detecting and imaging microscopic amounts of nanoparticles. We describe in detail procedures and parameters necessary for implementation of in vivo detection through the use of antibody-labelled magnetic nanoparticles as well as methods of determining magnetic nanoparticle properties. We discuss the weak field magnetic sensor SQUID system, the method of generating the magnetic polarization pulse to align the magnetic moments of the nanoparticles, and the measurement techniques to measure their magnetic remanence fields following this pulsed field. We compare these results to theoretical calculations and predict optimal properties of nanoparticles for in vivo detection.

IntroductionBreast cancer detection using mammography has improved clinical outcomes for many women, because mammography can detect very small (5 mm) tumors early in the course of the disease. However, mammography fails to detect 10 - 25% of tumors, and the results do not distinguish benign and malignant tumors. Reducing the false positive rate, even by a modest 10%, while improving the sensitivity, will lead to improved screening, and is a desirable and attainable goal. The emerging application of magnetic relaxometry, in particular using superconducting quantum interference device (SQUID) sensors, is fast and potentially more specific than mammography because it is designed to detect tumor-targeted iron oxide magnetic nanoparticles. Furthermore, magnetic relaxometry is theoretically more specific than MRI detection, because only target-bound nanoparticles are detected. Our group is developing antibody-conjugated magnetic nanoparticles targeted to breast cancer cells that can be detected using magnetic relaxometry.MethodsTo accomplish this, we identified a series of breast cancer cell lines expressing varying levels of the plasma membrane-expressed human epidermal growth factor-like receptor 2 (Her2) by flow cytometry. Anti-Her2 antibody was then conjugated to superparamagnetic iron oxide nanoparticles using the carbodiimide method. Labeled nanoparticles were incubated with breast cancer cell lines and visualized by confocal microscopy, Prussian blue histochemistry, and magnetic relaxometry.ResultsWe demonstrated a time- and antigen concentration-dependent increase in the number of antibody-conjugated nanoparticles bound to cells. Next, anti Her2-conjugated nanoparticles injected into highly Her2-expressing tumor xenograft explants yielded a significantly higher SQUID relaxometry signal relative to unconjugated nanoparticles. Finally, labeled cells introduced into breast phantoms were measured by magnetic relaxometry, and as few as 1 million labeled cells were detected at a distance of 4.5 cm using our early prototype system.ConclusionsThese results suggest that the antibody-conjugated magnetic nanoparticles are promising reagents to apply to in vivo breast tumor cell detection, and that SQUID-detected magnetic relaxometry is a viable, rapid, and highly sensitive method for in vitro nanoparticle development and eventual in vivo tumor detection.

Retinotopic mapping strategies similar to those used for invasive electrophysiological studies to identify multiple visual areas in monkeys have been adapted for noninvasive studies in humans, using magnetic recordings of brain activity in conjunction with anatomical magnetic resonance imaging. The retinotopic organization of the primary visual area (V1) in the left hemisphere of human subjects was examined by presenting a small patterned stimuli near the vertical and horizontal meridians in the lower right visual field. In contrast with the classical model of V1 retinotopy, our results suggest that the representation of the horizontal meridian does not necessarily correspond in a one-to-one manner with the base of the calcarine fissure and that some lower field stimuli can activate regions in the lower bank of the fissure. The results also indicate significant individual variability in the details of how V1 maps around the calcarine fissure.