Unlocking the Invisible: The Evolution and Impact of the Electron Microscope in Cell Biology

The electron microscope (EM) is one of the most essential instruments in biology, revolutionizing our understanding of cellular structure by allowing scientists to observe subcellular details that were previously invisible with traditional light microscopes (LM), which had been in use since the late sixteenth century.

A Glimpse into a Minuscule World

While the LM can magnify objects up to 2,000 times, the EM can magnify objects up to 2,000,000 times, offering far greater resolution. There are two main types of electron microscopes: the transmission electron microscope (TEM) and the scanning electron microscope (SEM). The TEM works by passing electrons through thin slices of tissue, producing two-dimensional images that allow for the examination of the internal structure of cells. On the other hand, the SEM scans the sample’s surface with an electron beam, providing detailed three-dimensional images of solid, living specimens, although its magnification power is roughly one-tenth that of the TEM and offers lower resolution.

However, the remarkable magnification capabilities of EMs come with significant drawbacks: they are extremely expensive to purchase and maintain; operators require extensive training to handle the equipment and prepare biological samples; specimens for the TEM must be stained and analyzed in a vacuum, meaning live samples cannot be studied; and the microscopes themselves are large and must be housed in vibration-free environments.

The EM was invented in 1931 at the University of Berlin by physicist Ernst Ruska and his professor, Max Knoll. Knoll had discovered that optical resolution (the ability to distinguish between two points) depends on the wavelength of the light source, and that the wavelength of electrons is 1/100,000th that of light waves. This insight led to the development of the first electron microscope, which used a focused beam of electrons to illuminate the specimen through electromagnets. The EM was further refined and commercialized by 1939, and in 1986, Ruska was awarded the Nobel Prize in Physics for his groundbreaking work. In the 1950s, George Palade, working at the Rockefeller Institute (now Rockefeller University), used the EM to uncover critical insights into the fundamental organization of cells, earning him the Nobel Prize in Medicine in 1974.

A scanning electron microscope can produce magnification up to 500,000 times. This SEM image of a flea—which is known to carry a number of diseases transmitted through its bites, including the bubonic plague, caused by the bacterium Yersinia pestis— has been artificially colorized.