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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. MRFM is potentially able to observe
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
structures which cannot be seen using
X-ray crystallography X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...
and
protein nuclear magnetic resonance spectroscopy Nuclear magnetic resonance spectroscopy of proteins (usually abbreviated protein NMR) is a field of structural biology in which NMR spectroscopy is used to obtain information about the structure and dynamics of proteins, and also nucleic acids, and ...
. Detection of the magnetic spin of a single
electron The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family, and are generally thought to be elementary particles because they have no kn ...
has been demonstrated using this technique. The sensitivity of a current MRFM microscope is 10 billion times greater than a medical MRI used in hospitals.


Basic principle

The MRFM concept combines the ideas of
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
(MRI) and
atomic force microscopy Atomic force microscopy (AFM) or scanning force microscopy (SFM) is a very-high-resolution type of scanning probe microscopy (SPM), with demonstrated resolution on the order of fractions of a nanometer, more than 1000 times better than the op ...
(AFM). Conventional MRI employs an inductive coil as an
antenna Antenna ( antennas or antennae) may refer to: Science and engineering * Antenna (radio), also known as an aerial, a transducer designed to transmit or receive electromagnetic (e.g., TV or radio) waves * Antennae Galaxies, the name of two collid ...
to sense resonant nuclear or electronic spins in a
magnetic field A magnetic field is a vector field that describes the magnetic influence on moving electric charges, electric currents, and magnetic materials. A moving charge in a magnetic field experiences a force perpendicular to its own velocity and to ...
gradient. MRFM uses a
cantilever A cantilever is a rigid structural element that extends horizontally and is supported at only one end. Typically it extends from a flat vertical surface such as a wall, to which it must be firmly attached. Like other structural elements, a canti ...
tipped with a
ferromagnetic Ferromagnetism is a property of certain materials (such as iron) which results in a large observed magnetic permeability, and in many cases a large magnetic coercivity allowing the material to form a permanent magnet. Ferromagnetic materials ...
(iron cobalt) particle to directly detect a modulated spin gradient force between sample spins and the tip. The magnetic particle is characterized using the technique of
cantilever magnetometry Cantilever magnetometry is the use of a cantilever to measure the magnetic moment of magnetic particles. On the end of cantilever is attached a small piece of magnetic material, which interacts with external magnetic fields and exerts torque on the ...
. As the ferromagnetic tip moves close to the sample, the atoms' nuclear spins become attracted to it and generate a small force on the cantilever. The spins are then repeatedly flipped, causing the cantilever to gently sway back and forth in a synchronous motion. That displacement is measured with an
interferometer Interferometry is a technique which uses the ''interference'' of superimposed waves to extract information. Interferometry typically uses electromagnetic waves and is an important investigative technique in the fields of astronomy, fiber op ...
(laser beam) to create a series of 2-D images of the sample, which are combined to generate a 3-D image. The interferometer measures resonant frequency of the cantilever. Smaller ferromagnetic particles and softer cantilevers increase the
signal-to-noise ratio Signal-to-noise ratio (SNR or S/N) is a measure used in science and engineering that compares the level of a desired signal to the level of background noise. SNR is defined as the ratio of signal power to the noise power, often expressed in deci ...
. Unlike the inductive coil approach, MRFM sensitivity scales favorably as device and sample dimensions are reduced. Because the signal-to-noise ratio is inversely proportional to the sample size, Brownian motion is the primary source of noise at the scale in which MRFM is useful. Accordingly, MRFM devices are
cryogenically In physics, cryogenics is the production and behaviour of materials at very low temperatures. The 13th IIR International Congress of Refrigeration (held in Washington DC in 1971) endorsed a universal definition of “cryogenics” and “cr ...
cooled. MRFM was specifically devised to determine the structure of
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
''in situ''.


Milestones

The basic principles of MRFM imaging and the theoretical possibility of this technology were first described in 1991. The first MRFM image was obtained in 1993 at the IBM Almaden Research Center with 1-μm vertical resolution and 5-μm lateral resolution using a bulk sample of the paramagnetic substance
diphenylpicrylhydrazyl DPPH is a common abbreviation for the organic chemical compound 2,2-diphenyl-1-picrylhydrazyl. It is a dark-colored crystalline powder composed of stable free radical molecules. DPPH has two major applications, both in laboratory research: one is ...
. The spatial resolution reached
nanometer 330px, Different lengths as in respect to the molecular scale. The nanometre (international spelling as used by the International Bureau of Weights and Measures; SI symbol: nm) or nanometer (American and British English spelling differences#-re ...
-scale in 2003. Detection of the magnetic spin of a single electron was achieved in 2004. In 2009 researchers at IBM and Stanford announced that they had achieved resolution of better than 10 nanometers, imaging tobacco mosaic virus particles on a nanometer-thick layer of adsorbed hydrocarbons.


References


External links

*University of Washington Quantum System Engineering and MRFM Home Page, https://web.archive.org/web/20060430032748/http://courses.washington.edu/goodall/MRFM/. *Magnetic-Resonance Force Microscopy, http://www.medgadget.com/archives/2005/04/magneticresonan.html. * ** * *Review Article: M. Poggio and C. L. Degen, Nanotechnology 21, 342001 (2010), {{SPM2 Scanning probe microscopy Nuclear magnetic resonance Protein structure