The first operative electron microscope was built in 1933 by German scientists Ernst Ruska and Max Knoll. Ruska and Knoll's microscope demonstrated all the principles of an electron microscope but could only magnify objects up to four hundred times. Further experiments later produced an electron microscope with resolution superior to a traditional optical microscope. In 1938, James Hillier and Albert Prebus, graduate students at the University of Toronto, created the first practical commercial electron microscope based on the work of Ruska and Knoll.

The electron microscope uses a particle beam of electrons to illuminate a sample and thus create a highly magnified image. Far superior to traditional light microscopes, modern electron microscopes utilize electromagnetic radiation and can magnify objects up to two million times. The electron microscope is capable of greater resolution and magnification because of the electron's wavelength, which is much smaller than that of a photon. The electron microscope controls an electron beam using electrostatic and electromagnetic lenses to form an image by focusing the beam at a specific plane relative to the sample in much the same way that an optical microscope uses glass lenses to focus light on or through a specimen to form an image.

Although modern electron microscopes can magnify objects up to two million times, they are still based upon Ruska's prototype, later perfected by Hillier and Prebus. The electron microscope has become an essential piece of equipment in many hospitals and laboratories around the world. Such microscopes are used to examine biological materials (such as microorganisms and cells) and a variety of large molecules, to detect cancer or tumors in humans and animals, and to examine metals and crystalline structures as well as the characteristics of various surfaces. More recent applications of the electron microscope include its use in inspection and quality assurance in industry, particularly semiconductor device fabrication.

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