March 12, 2009

Magnetic resonance force microscopy

Magnetic resonance force microscopy (MRFM) is an imaging technique that acquires magnetic resonance images (MRI) at nanometer scales, and possibly at atomic scales in the future.

IBM and Stanford combined ultrasensitive magnetic resonance force microscopy (MRFM) with 3D image reconstruction to achieve magnetic resonance imaging (MRI) with resolution <10 nm. [4 nanometers]

The image reconstruction converts measured magnetic force data into a 3D map of nuclear spin density, taking advantage of the unique characteristics of the “resonant slice” that is projected outward from a nanoscale magnetic tip. The basic principles are demonstrated by imaging the 1H spin density within individual tobacco mosaic virus particles sitting on a nanometer-thick layer of adsorbed hydrocarbons. This result, which represents a 100 million-fold improvement in volume resolution over conventional MRI, demonstrates the potential of MRFM as a tool for 3D, elementally selective imaging on the nanometer scale.

Scientists from Stanford and IBM have improved the sensitivity of magnetic resonance imaging by 100 million times using a new technique for measuring tiny magnetic forces. The sensitivity improvement allowed a dramatic improvement of resolving power, achieving a resolution down to 4 nanometers (nm).

As for the future of MFRM technology, both researchers have high hopes. "I envision a machine, similar to the one we have today, in which we load a new protein or molecule, whose structure we don't know, every month or so," said Poggio. "In that time we make a detailed atomic-scale image of the protein or molecule.

"If we are able to obtain 10 to 100 times finer resolution, MRFM would truly represent a breakthrough for structural biologists."

MRFM is chemically selective, meaning that it can be used to look at a variety of elements to obtain a more detailed picture of the sample's structure. "For example, if you wanted to see where the DNA is, you can tune in to phosphorous," said Rugar.

Each scan takes several days and must be conducted in a super-cooled vacuum.

With further progress in resolution and sample preparation, force-detected MRI techniques could have significant impact on the imaging of nanoscale biological structures, even down to the scale of individual molecules. Achieving resolution <1 nm seems realistic because the current apparatus operates almost a factor of 10 away from the best demonstrated force sensitivities and field gradients.

Even with a resolution >1 nm, MRFM may allow the basic structure of large molecular assemblies to be elucidated. One can imagine enhancing MRFM image contrast beyond the basic spin-density information by using techniques similar to those developed for clinical MRI and NMR spectroscopy. Such contrast may include selective isotopic labeling (for example, substituting 1H with 2H), selective imaging of different chemical species (like 13C, 15N, or 31P), relaxation-weighted imaging, and spectroscopic imaging that reflects the local chemical environment. Some techniques, such as cross-polarization and depolarization between different nuclear spin species, have already been demonstrated for MRFM on the micrometer scale. At the nanometer scale, the ability to target and locate specific proteins although selective labeling, for example, could allow direct 3D imaging of the organization and structure of multicomponent macromolecular complexes. Such a capability would be complementary to current techniques, such as cryoelectron microscopy, and could develop into a powerful tool for structural biology.

The virus particles used as samples sit on an extremely flexible microscopic cantilever, which Rugar describes as a "little silicone diving board."

Then, using an oscillating magnetic field, researchers "flip the direction of the nuclear spin."

Bringing another tiny magnet close to the spinning particles will produce either an attractive or repulsive force that is measured by vibrations in the cantilever.

By measuring forces generated as the tiny magnet is positioned at 8,000 different points around the sample, scientists can generate a three-dimensional map of hydrogen density, thereby creating a three-dimensional image.

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