NanoMRI and the Quest for a Molecular Structure Microscope - overview

Can a microscope be developed that has the capability to directly image the three dimensional atomic structure of individual biomolecules? This is the question that drives the work at IBM on nanoscale magnetic resonance imaging.

Throughout the history of microscopy, new techniques have been sought to allow exploration of smaller and smaller objects with increasingly better resolution and functionality. This evolution in imaging has taken us from light microscopes all the way to techniques such as scanning tunneling microscopy, which in many cases is able to image the individual atoms on a surface. However, no technique yet developed can image the full three-dimensional structure of macromolecules (like proteins) with sufficient resolution to directly resolve the 3D atomic structure. Developing such a technique would have revolutionary impact on fields such as structural biology and nanotechnology.

Magnetic resonance imaging (MRI) is well-known in medicine as a non-destructive technique that is able to look inside objects in three dimensions, with resolution typically in the millimeter to sub-millimeter range. The ability of MRI to take images at higher resolution, however, has been limited by the fundamental sensitivity limitations of coil-based inductive detection. Consequently, the best resolution using conventional MRI techniques corresponds to a volume element (voxel) that is approximately 3 micrometers on a side. To overcome this resolution limit, Prof. John Sidles at University of Washington proposed an alternative detection method, called "magnetic resonance force microscopy" or MRFM.1 MRFM overcomes the sensitivity limitations of inductive detection by using the ultrasensitive detection of magnetic forces. IBM has led the effort in developing MRFM techniques, starting with the earliest demonstrations.2,3

The ultimate goal of the work at IBM is to develop a "molecular structure microscope" based on MRFM with the capability to directly image the 3D atomic structure of macromolecules. Working toward this long term goal, IBM has recently shown that MRFM can improve the sensitivity of MRI by a factor of 100 million, culminating in the demonstration of 3D imaging of individual virus particles with 4 nm resolution.5 Here is a link to the paper published in the Proceedings of the National Academy of Sciences:
The paper was accompanied by an IBM press release: Release 1

In previous work, IBM also demonstrated that MRFM is sensitive enough to detect the magnetism of a single electron spin.4 Release 2/

Selected References for Magnetic Resonance Force Microscopy

  1. J. A. Sidles. Folded Stern-Gerlach experiment as a means for detecting nuclear magnetic resonance in individual nuclei. Phys. Rev. Lett. 68, 1124-1127 (1992).
  2. D. Rugar, C. S. Yannoni & J. A. Sidles. Mechanical detection of magnetic resonance. Nature 360, 563-566 (1992).
  3. D. Rugar, O. Zuger, S. Hoen, C. S. Yannoni, H. M. Vieth & R. D. Kendrick. Force detection of nuclear magnetic resonance. Science 264 1560-1563 (1994).
  4. D. Rugar, R. Budakian, H. J. Mamin & B. W. Chui. Single spin detection by magnetic resonance force microscopy. Nature 430, 329-332 (2004).
  5. C. L. Degen, M. Poggio, C. Rettner, H. J. Mamin & D. Rugar. Nanoscale magnetic resonance imaging. Proc. Nat. Acad. Sci. 106, 1313-1317 (2009).

The MRFM Instrument

Link to the MRFM Instrument

The MRFM Cantilever

Link to MRFM Cantilever

3D Nano-MRI of Tobacco Mosaic Virus

Link to 3D Nano-MRI of Tobacco Mosaic Virus

The MRFM Scientists

Link to MRFM Scientists