We will develop a prototype inverted SQUID (Superconducting Quantum Interference Device) microscope for neuroscience research. The signal levels are expected to be much weaker (100-500 ftrms, ft = 10/-15 Tesla) than signals in the area of non-destructive evaluation (> 1 pT, pT= 10/-12 Tesla) where SQUID microscopes have been used previously. Therefore, in Phase I we have determined the feasibility of constructing an ultasensitiveSQUID microscope. We have shown that a magnetometer-SQUID assembly with a submillimeter diameter pickup coil can be constructed with a noise level of about 70 fTrms/VHz that meets one of our design criteria set forth in our Phase I objectives. We have also determined the minimum thickness of the sapphire window that will serve as the barrier between the sample at atmospheric pressure and the SQUID sensors in vacuum. Based on these results, we expect that it should be possible to build an inverted SQUID microscope sufficiently sensitive for neuroscience research.
In Specific Aim 1, we will construct a prototype with a 8-channel magnetometer-SQUID sensory array, each magnetometer being about 0.6 mm in diameter with a field sensitivity around 70 fTrms/VHz or better with the detection coils at a distance of 200 mu/m away from neurons and glial cells to be studied. The microscope is similar to an inverted optical microscope except the objective is replaced by an array of superconducting miniature magnetic field sensing coils.
In Specific Aim 2, we will test the microscope in an experimental setting in order to evaluate its utility in neuroscience research. First, the field sensitivity (in fT/VHz) will be determined in a magnetically shielded room without any sample. Once the system noise level is determined to be within the specified level, it will be used to measure magnetic fields produced by a neocortical slice. We will determine the signal levels from the slice and compare with our predictions. Agreements between the observed and predicted values will indicate that the microscope should be useful for other applications that will include measurements of: (1) electrical currents from single neurons and glial cells in culture, (2) efficiency of bonding of antigens and magnetically tagged antibodies (immunoassay), and (3) movements and conformational changes of a small number of magnetically tagged molecules in a cell for studying signaling pathways. The proposed SQUID microscope should be useful in both academic setting and industry for understanding the electrophysiology of small cells that are difficult to study with electrodes, for drug discovery and for studying second-messenger systems.
