Electron microscope, transmission and scanning

Described by the Nobel Society as "one of the most important inventions of the century," the electron microscope is a valuable and versatile research tool. The first working models were constructed by German engineers Ernst Ruska and Max Knoll in 1932, and since that time, the electron microscope has found numerous applications in chemistry, engineering, medicine, molecular biology and genetics.

Electron microscopes allow molecular biologists to study small structural details related to cellular function. Using an electron microscope, it is possible to observe and study many internal cellular structures (organelles). Electron microscopy can also be used to visualize proteins, virus particles, and other microbiological materials.

At the turn of the twentieth century, the science of microscopy had reached an impasse: because all optical microscopes relied upon visible light, even the most powerful could not detect an image smaller than the wavelength of light used. This was tremendously frustrating for physicists, who were anxious to study the structure of matter on an atomic level. Around this time, French physicist Louis de Broglie theorized that subatomic particles sometimes act like waves, but with much shorter wavelengths. Ruska, then a student at the University of Berlin, wondered why a microscope couldn't be designed that was similar in function to a normal microscope but used a beam of electrons instead of a beam of light. Such a microscope could resolve images thousands of times smaller than the wavelength of visible light.

There was one major obstacle to Ruska's plan, however. In a compound microscope, a series of lenses are used to focus, magnify, and refocus the image. In order for an electron-based instrument to perform as a microscope, some device was required to focus the electron beam. Ruska knew that electrons could be manipulated within a magnetic field, and in the late 1920s, he designed a magnetic coil that acted as an electron lens. With this breakthrough, Ruska and Knoll constructed their first electron microscope. Though the prototype model was capable of magnification of only a few hundred power (about that of an average laboratory microscope), it proved that electrons could indeed be used in microscopy.

The microscope built by Ruska and Knoll is similar in principle to a compound microscope. A beam of electrons is directed at a specimen sliced thin enough to allow the beam to pass through. As they travel through, the electrons are deflected according to the atomic structure of the specimen. The beam is then focused by the magnetic coil onto a photographic plate; when developed, the image on the plate shows the specimen at very high magnification.

Scientists worldwide immediately embraced Ruska's invention as a major breakthrough in microscopy, and they directed their own efforts toward improving upon its precision and flexibility. A Canadian-American physicist, James Hillier, constructed a microscope from Ruska's design that was nearly 20 times more powerful. In 1939, modifications made by Vladimir Kosma Zworykin enabled the electron microscope to be used for studying viruses and protein molecules. Eventually, electron microscopy was greatly improved, with microscopes able to magnify an image 2,000,000 times. One particularly interesting outcome of such research was the invention of holography and the hologram by Hungarian-born engineer Dennis Gabor in 1947. Gabor's work with this three-dimensional photography found numerous applications upon development of the laser in 1960.

There are now two distinct types of electron microscopes: the transmission variety (such as Ruska's), and the scanning variety. The Transmission Electron Microscope (TEM), developed in the 1930's, operates on the same physical principles as the light microscope but provides enhanced resolution due to the shorter wavelengths of electron beams. TEM offers resolutions to approximately 0.2 nanometers as opposed to 200 nanometers for the best light microscopes. The TEM has been used in all areas of biological and biomedical investigations because of its ability to view the finest cell structures. Scanning electron microscopes (SEM), instead of being focused by the scanner to peer through the specimen, are used to observe electrons that are scattered from the surface of the specimen as the beam contacts it. The beam is moved along the surface, scanning for any irregularities. The scanning electron microscope yields an extremely detailed three-dimensional image of a specimen but can only be used at low resolution; used in tandem, the scanning and transmission electron microscopes are powerful research tools.

Today, electron microscopes can be found in most hospital and medical research laboratories.

The advances made by Ruska, Knoll, and Hillier have contributed directly to the development of the field ion microscope (invented by Erwin Wilhelm Muller) and the scanning tunneling microscope (invented by Heinrich Rohrer and Gerd Binnig), now considered the most powerful optical tools in the world. For his work, Ruska shared the 1986 Nobel Prize for physics with Binnig and Rohrer.

See also Biotechnology; Laboratory techniques in immunology; Laboratory techniques in microbiology; Microscope and microscopy; Molecular biology and molecular genetics