In a recent series of articles, Sidles 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 experiment are replaced by the """"""""folded"""""""" trajectory of a micron-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 molecular structure. More recently, Dan Rugar and Nino Yannoni of IBM Almaden Laboratories, in collaboration with Dr. Sidles, 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 stimulate the development of practical instruments for imaging individual biological molecules in situ. The proposed imaging technology would be nondestructive, fully three-dimensional, and would achieve subangstrom spatial resolution. Should this broad objective be achieved, direct molecular imaging would become a primary tool for structural studies in molecular biology. In many health-related areas, such as the rational design of antiviral agents, the pace of research would be substantially accelerated. Pursuant to this overall objective, the specific aims of the proposed research are: (1) To further develop the theory of oscillator-coupled magnetic resonance. (2) To generate feasibility studies for two new kinds of force microscope: (a) Low-risk devices for imaging micron-scale samples. (b) Advanced devices for imaging single-copy molecules. (3) To collaborate with other researchers at universities, national laboratories, and private companies in identifying opportunities for applying this new technology.
