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Robert Hooke once poignantly stated that “by the help of microscopes, there is nothing so small, as to escape our inquiry; hence there is a newly visible world discovered to the understanding”. Developments in microscopy have furthered our understanding of many diseases over the last 300 years.
When considering the history of any type of the microscope, the origin can be traced back over 300 years to the invention of the first compound “microscope” by Galileo Galilei, and later to the work and inventions of Antony can Leeuwenhoek, widely considered to be the pioneering father of microscopy.
Van Leeuwenhoek’s microscope consisted of a single powerful lens that was used to observe samples suspended on the tip of a pin. Through this, he was able to observe and characterize the cells of plants and the surface appearance of a red blood cell amongst other samples.
The invention of the electron microscope was built on these ground-breaking discoveries and brought with it the possibility of viewing a whole new world. It was eventually refined down to the molecular and then atomic level. This was revolutionary for almost every field of biological and materials science.
The Roaring Twenties brought with them more than social hedonism. During this decade, the understanding that accelerated electrons behave in a similar way to light when in a vacuum was a revolutionary discovery.
Additionally, both magnetic and electric fields could be used to manipulate the path of moving electrons, in the same way mirrors can refract light. Building on this, in 1926 Hans Busch invented the first electromagnetic lens, and supposedly patented the first designs for the electron microscope using this invention.
In 1931, Ernst Ruska and Max Knoll from Berlin University built the first Transmission Electron Microscope, capable of magnifying to 400 power. At the time this was ground-breaking, far out shadowing the capabilities of standard light microscopes, although it pales in comparison to the power of current-day TEMs. It was not until 1986, over half a century later, that Ruska was awarded the Nobel Prize in the field of physics for his work in developing this trailblazing piece of technology.
Later that same year, the scientific director of Siemens-Schuckertwerke, a Berlin-based electrical company, Reinhold Rudenberg purchased the patent for Busch’s design. Several years passed and in 1936 the noted physicist Bodo von Borries teamed up with Hemut Ruska and Rudenberg to further the potential applications of the TEM in different fields of science. Two years later, the first TEM was marketed to the scientific community by Siemens-Schuckertwerke.
Lense quality and electron accelerator power dramatically increased over this time period, allowing for the improvement of imaging. Between 1931 and 1945 the theoretical resolution of TEMs increased from sub-50 Angstrom (1nm=10 Angstrom units) to 2nm, surpassing that of the traditional brightfield, or light, microscope a hundred-fold. SEMs' resolution also increased from a starting point of 200 Angstroms - today, a standard resolution is around 10nm.
By 1948, Cambridge University's Engineering Department had coordinated their first SEM, and within four years, it was producing 3D images. The idea was to produce a SEM for the market that was cheaper with a greater magnifying power and the ability to be used in many different industries. Today, there are over 50,000 SEMs being used in classrooms and labs worldwide.
Between 1960 and 1990 developments and modifications to the design of the electron microscope permitted more advanced techniques. The incorporation of an adjustable sample mount allowed researchers to begin shadowing samples, a technique that involves placing specimens at an angle oblique to the electron beam. Electron shadowing ensures one section of the sample receives greater electron exposure and therefore will hopefully have greater definition in the resulting image.
In more recent years the history of electron microscopes is documented in the scientific discoveries they have enabled. Notably, the electron microscope is the only form of technology which can visualize molecules, viruses, and atoms.
Thousands of viral strains have been physically characterized, including the Hepatitis C virus which was first imaged in 2016 owing to the use of a TEM. As such, the electron microscope was and continues to be one of the greatest scientific breakthroughs in history.