Biological applications of the SQUID microscope

The recently developed “microscope” based on a high-T _c dc SQUID (Superconducting QUantum Interference Device) is used to detect the magnetic fields produced by biological samples maintained at room temperature and atmospheric pressure. The microscope consists of a SQUID placed on the end of a sapphire “cold finger” thermally anchored to a liquid nitrogen reservoir inside a vacuum enclosure. A 3-μ m thick silicon nitride (SiN) membrane, located above the SQUID, acts as a vacuum window. Room temperature samples are placed on top of the window and can be brought within 15μm of the SQUID.; In Part I, the SQUID microscope is used to investigate magnetotactic bacteria, microorganisms which possess a permanent dipole moment. The magnetic field produced by the motion of the bacteria in growth medium is detected by the SQUID in the microscope. Measurements are performed on both motile and nonmotile bacteria. In the nonmotile case, we obtain the power spectrum of the magnetic flux noise produced by the rotational Brownian motion of the ensemble of bacteria. Furthermore, we measure the time-dependent flux produced by the ensemble in response to an applied uniform magnetic field. In the motile case, we obtain the magnetic flux power spectra produced by the swimming bacteria. Combined, these measurements determine the average rotational drag coefficient, magnetic moment, and the frequency and amplitude of the vibrational and rotational modes of the bacteria in a unified set of measurements. In addition, the microscope can easily resolve the motion of a single bacterium. This technique can be extended to any biological substance to which a suitable magnetic label can be attached.; In Part II, a technique is described for the specific, sensitive, quantitative, and rapid detection of biological targets using superparamagnetic nanoparticle labels. In this technique, a mylar film to which the targets have been bound is placed on the microscope, typically 40μm from the SQUID. A suspension of magnetic nanoparticles carrying antibodies directed against the target is added to the mixture in the well, and one-second pulses of magnetic field are applied parallel to the SQUID. In the presence of this aligning field the nanoparticles develop a net magnetization, which relaxes when the field is turned off. Unbound nanoparticles relax rapidly by Brownian rotation and contribute no measurable signal. Nanoparticles that are bound to the target on the film are immobilized and undergo Néel relaxation, producing a slowly decaying magnetic flux which is detected by the SQUID. The ability to distinguish between bound and unbound labels allows one to run homogeneous assays, which do not require separation and removal of unbound magnetic particles. The technique has been demonstrated with a model system of liposomes carrying the FLAG epitope. The SQUID microscope requires no more than (5 ± 2) × 104 magnetic nanoparticles to register a reproducible signal.; Improvements to the SQUID microscope designed to increase its sensitivity are discussed. An experiment is proposed in which the microscope is used as a single molecule probe, detecting a single magnetic label attached to a biological macromolecule like DNA.