Micromechanical Oscillators for Imaging Molecules by Magnetic Resonance Force Microscopy

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9318002 Garbini A recent series of articles by Joe Garbini, John Sidles, and Gary Drobny of the University of Washington has described a new method for imaging individual molecules. The proposed imaging technology is based on a variation of the Stern- Gerlach experiment, in which the linear particle trajectories of the classic Stern-Gerlach experiment are replaced by the "folded" trajectory of a micrometer-scale mechanical oscillator. In theory, this new approach to magnetic resonance imaging combines the single-particle sensitivity of the Stern- Gerlach experiment, the nondestructive 3D imaging capability of magnetic resonance, and the subAngstrom spatial resolution of scanning probe techniques. It might therefore serve as the basis of a technology for imaging biomolecular structure. More recently, Dan Rugar and Nino Yannoni of IBM Almaden Laboratories have reported the first experimental detection of magnetic resonance by force microscope means. It is noteworthy that this first experiment achieved a room- temperature sensitivity comparable to the best available room-temperature inductive coils. The broad objective of the proposed research is to develop practical instruments for imaging individual biological molecules in situ. This imaging technology would be nondestructive, fully three-dimensional, and would achieve subAngstrom spatial resolution. Published theoretical work indicates that successful molecular imaging will require a force sensitivity of approximately 10-19 N/Hz. In comparison, the room- temperature cantilever in the UW/IBM experiment experimentally demonstrated a sensitivity of 10-15 N/Hz. One goal of the proposed research is to attain a sensitivity of 10-17N/Hz suing commercially available cantilevers. On a logarithmic scale, this represents progress half-way toward the overall goal of developing a practical molecular imaging technology. As discussed in the body of this proposal, it is reasonable to expect substantial impro vements in sensitivity from: (1) operating a t cryogenic temperatures (3-10K), instead of room temperature, (2) operating in a high vacuum, as opposed to a millitorr vacuum, (3) removing the gold metallic coating from the cantilever, (4) baking surface contaminants off the cantilever, (5) annealing the cantilever material to reduce dislocation density. A primary focus of our research is to do these experiments, which will serve to establish a reliable and experimentally validated understanding of noise mechanical oscillators. This applied knowledge base will serve as the necessary foundation for developing a practical biomolecular imaging technology. A more fundamental objective of our program is to establish a reliable and experimentally validated understanding o noise mechanisms in microscale mechanical oscillators. This applied knowledge base will serve as the necessary foundation for developing a practical biomolecular imaging technology. There reasonable scientific grounds to expect that the next generation o molecular biologist will routinely, quickly, and easily obtain images showing the full three-dimensional structure of the molecules they are studying, in situ, with all their ligands, cross-links, and glycosylation in place. This structural imaging capability, if it can be achieved, will complement and enhance the value of existing instruments for the rapid sequencing of genes and proteins, by providing a structural context for interpretation of sequence information. Our hope is that this will substantially accelerate the development of effective treatments for presently intractable disorders.