High Resolution SQUID Magnetometer for Imaging Biological Systems

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The objective of the proposed research is to develop ultra-high resolution, Superconducting QUantum Interference Device (SQUID) magnetometers (UHRSM) that are optimized for the imaging of the magnetic fields produced by action currents, remanent magnetization, and magnetic susceptibility in isolated living tissue and small experimental animal preparations at the scale of 100m.. Such measurements are not yet in wide spread use, primarily because of the limitations and costs of existing instrumentation. This project is designed specifically to address these points. The proposed instruments will be capable of making measurements that are impossible with any other technique, and should lead to new insights into cellular biology and electrophysiology. As they are being developed, these instruments will be immediately incorporated into the electrophysiological research on cardiac muscle, nerves, and intestinal smooth muscle that is ongoing at Vanderbilt, and will be made available to collaborators from other institutions. The proposed research involves the staged development of the cryostats, SQUIDs, and vacuum windows required for a high-sensitivity UHRSM utilizing a liquid-helium-cooled, low-temperature superconductivity (LTS) SQUID, and a lower sensitivity, higher resolution UHRSM with a liquid-nitrogen-cooled, high-temperature superconductivity (HTS) SQUID. The first system will use hand-wound pickup coils, a commercially-packaged LTS SQUID, and a custom-built, continuous-flow cryostat that should provide a semi- automatic system not requiring periodic helium and nitrogen transfers. The more advanced versions will utilize custom LTS and HTS SQUID gradiometers and magnetometers mounted in inexpensive commercial dewars designed for infrared spectroscopy. While this is under development, specialized LTS SQUIDs with on-chip pickup coils will be fabricated at Hypres at no cost to NSF. Apodization and other coil design techniques will be used , to develop arrays of SQUIDs whose pickup coils are optimized for high- resolution biomagnetic j imaging and inverse calculations of the current and magnetization distributions in the biological samples. Digital SQUIDs will be provided by Hypres for evaluation. These instruments are based upon proven cooling and vacuum- window technologies; the challenge lies in integrating these with optimized SQUID magnetometers to create user-friendly, inexpensive magnetic microscopes. These instruments will be unique in their ability to measure quantitatively magnetic fields at the near-cellular level. While electrical measurements of neural and cardiac tissue have been explored extensively over the past century, only in the past few years has it been possible to use SQUIDs to image cellular action currents. High resolution magnetic susceptibility imaging has yet to be applied to biological systems. Many biological phenomena involving electrical cell-to-cell communication and non-uniform propagation, such as those that are key to the behavior of cardiac~ihuscle and intestinal smooth muscle, are governed by the transfer of electrical charge. Since the distributed electrical resistivity and capacitance of these systems is often unknown or poorly characterized, electrical measurements alone cannot suffice to quantify this charge transfer. Hence direct measurements of current are crucial to understanding cell-to-cell coupling. More importantly, the combination of magnetic measurements of current and electrical and optical measurements of voltage offers unique promise towards improving the understanding of not only th e transfer of charge between cells but also the tissue properties that relate current to voltage. Other biological applications include the study of cortical oscillations, spreading depression, action currents in algae and higher plants, iron biominerals in living systems, and magnetic tracers. The proposed program of instrumentation development, coupled with an aggressive program of biophysical measurements, should advance the ability to study the electrical behavior of cellular systems and their response to physical and pharmacological interventions.