The Scanning Probe Microscope: the most versatile of microscopes

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The scanning probe microscope is probably the most versatile of all microscopes. There is scarcely a physical property of matter that cannot be investigated with scanning tunnelling, scanning probe and atomic force microscopes: material properties as diverse as magnetism, capacitance, surface potential, thermal, acoustics, etc, all have a variant of an SPM developed specifically for their study.

And now, with the development of softer cantilevers and nanoscale tips for AFMs, the biologist has a tool to investigate the functional properties of cells and macromolecules in their native state in physiological conditions. Ion conductance microscopes can be used to measure ion currents of membrane channel proteins in neurons, and atomic force microscopes characterize intermolecular forces of receptors and their ligands.

The double helix is a motif commonly found in nature: two spirals of matter with a common axis have been seen inter alia in nebulae in outerspace, intertwined plant stems, the amylopectins of pasta, inorganic crystals, and of course in our genetic material DNA.  The elegant double helix staircase, designed by Leonardo da Vinci, is one of the architectural features of the Chateau Chambord in France, and its motif is replicated in a staircase in the Chemistry Department of my alma mater, the University of Reading.

Microscopy has been an essential tool for molecular biologists. The double helix structure of DNA was famously revealed in images produced by X-ray diffraction. The existence of exons (coding regions) and introns (non-coding regions) was established when messenger RNA, the nucleic acid that binds to ribosomes and directs the synthesis of proteins, was hybridized to its source DNA and examined in the transmission electron microscope: there were many regions of the DNA that did not bind hybridize, forming loops of introns.

With the advent of the scanning probe microscope, molecular biologists now have another tool in their arsenal to characterize the structure and properties of biological macromolecules. Soft cantilevers can reveal the double helix of DNA in its native state in physiological solutions. By using a functionalized tip that binds to any of the four DNA types bases, the AFM can now be used to sequence DNA.

The van der Waals force is the product of the attractive or repulsive forces between molecules other than those due to covalent and hydrogen bonds, or electrostatic interaction. Although weak, these forces are key to the functioning of an atomic force microscope. At a distance of only a few nanometers, the van der Waals forces are strong enough to deflect a cantilever tip. Recently, this has allowed  the use of chemical force measurements as the basis for atomic recognition of silicon, tin and lead on the surfaces of alloys, thus adding elemental composition to the repertoire of scanning probe microscopy.

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