Wikipedia Deep Dive

Electron microscope

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In 1931, two German researchers built a machine that could see things a hundred thousand times smaller than the width of a human hair. To put that in perspective: if you held a strand of your hair up to a regular microscope, you'd see it clearly. But the viruses crawling on that hair? Invisible. The atoms making up those viruses? Laughably beyond reach. Ernst Ruska and Max Knoll changed all of that. They figured out how to use electrons—the same tiny particles that flow through the wires powering your home—as a kind of light source for microscopes. And in doing so, they cracked open a door to an entirely new world.

This is a story about seeing the unseeable.

Why Light Isn't Enough

To understand why electron microscopes matter, you first need to understand why regular microscopes fail.

Ordinary microscopes use light. You shine light through a thin slice of something—a leaf, a drop of pond water, a sliver of human tissue—and lenses bend that light to magnify what you're looking at. It works beautifully for cells, bacteria, even some larger viruses. But there's a fundamental physical limit built into this approach, and it has nothing to do with how good your lenses are.

Light travels in waves. And waves have a property called wavelength—essentially, the distance between one peak of the wave and the next. Visible light, the kind your eyes can detect, has wavelengths between about 400 and 700 nanometers. Here's the problem: you cannot use a wave to see anything smaller than that wave's own wavelength. It's like trying to measure the width of a grain of sand using a ruler where the smallest marking is one inch. The physics simply don't allow it.

This means light microscopes hit a wall at about 200 nanometers of resolution. That sounds impressively small—200 nanometers is about a thousand times thinner than a human hair—but it's nowhere near small enough to see the architecture of individual molecules, the lattice of atoms in a crystal, or the structural details of the proteins that make up a vaccine.

Electrons offered a way around this wall. As it turns out, electrons also behave like waves, a strange quantum mechanical fact that Einstein and de Broglie helped establish in the early twentieth century. But electron waves are extraordinarily short—up to a hundred thousand times shorter than visible light. Use electrons instead of light, and suddenly your theoretical resolution plunges down to about 0.1 nanometers. That's roughly the size of a single atom.

Building the First Electron Eyes

The path to the first electron microscope was neither straight nor free of controversy.

By the late 1920s, physicists had figured out most of the pieces they would need. Heinrich Hertz had shown back in 1883 that you could steer beams of electrons using electric and magnetic fields—this was the technology behind early cathode ray tubes, the ancestors of old television sets. Emil Wiechert demonstrated in 1899 that magnetic fields could focus electrons, bending them the way glass lenses bend light. And in 1926, Hans Busch worked out the mathematical theory of electromagnetic lenses, showing precisely how to use magnetic coils to focus an electron beam to a sharp point.

The question was: could anyone assemble these pieces into a working microscope?

At the Technical University of Berlin, a professor named Adolf Matthias had assembled a research team to study electron beams and cathode-ray oscilloscopes. He put Max Knoll, a skilled electrical engineer, in charge. Knoll recruited several doctoral students, including a quiet young physicist named Ernst Ruska.

In 1931, Knoll and Ruska achieved something remarkable. They built a device with two electromagnetic lenses arranged in sequence—one to focus the electron beam, another to magnify the resulting image—and used it to produce magnified images of simple metal mesh grids. The magnification wasn't impressive by later standards, but the principle was proven. You could use electrons to see.

Two years later, in 1933, they built an improved version that finally exceeded the resolution of optical microscopes. The electron microscope had arrived.

Or had it?

Reinhold Rüdenberg, an engineer working at the industrial giant Siemens, had filed patents for an electron microscope in 1932. The patents predated the Knoll-Ruska publications, and Rüdenberg claimed his team had been working on the technology independently for years. According to patent law, this made Rüdenberg the official inventor. But whether Siemens actually had a working instrument before the Berlin university team remains unclear to this day.

The Nobel committee eventually sided with Ruska, awarding him the 1986 Nobel Prize in Physics for his work on electron optics and the design of the first electron microscope. By then, both Knoll and Rüdenberg had died—Knoll in 1969, Rüdenberg in 1961—making them ineligible to share in the recognition.

From Laboratory Curiosity to Scientific Workhorse

The first electron microscopes were finicky, expensive, and extraordinarily difficult to use. But their potential was immediately obvious.

Siemens recognized this early. In 1937, the company hired Ernst Ruska and another physicist named Bodo von Borries to develop practical electron microscopes. They also brought on Ernst's brother, Helmut Ruska, specifically to figure out how to use the technology for biological research. That same year, Manfred von Ardenne invented a different approach called the scanning electron microscope, which we'll return to shortly.

By 1938, Siemens had produced the first commercial electron microscope. A year later, they released a transmission electron microscope—the design that Ruska had pioneered—capable of magnifications far beyond anything previously possible.

Meanwhile, researchers in North America were racing to catch up. At Washington State University, Anderson and Fitzsimmons built one of the first American electron microscopes. At the University of Toronto, physicist Eli Franklin Burton led a team that included Cecil Hall, James Hillier, and Albert Prebus in constructing their own instrument. Hillier would go on to have a distinguished career developing electron microscopes at RCA, making them smaller, more stable, and more practical for everyday laboratory use.

The technology improved rapidly through the 1940s and 1950s. Higher resolution. Better stability. More reliable electron sources. By the time vaccines became a routine part of public health in the mid-twentieth century, electron microscopes had become essential tools for understanding what, exactly, those vaccines were fighting against.

Two Ways of Seeing

Modern electron microscopes come in two fundamental varieties, and understanding the difference between them explains a lot about how scientists study the invisible world.

The first type, and historically the oldest, is the transmission electron microscope, usually abbreviated as TEM. It works on the same basic principle as a slide projector. You take a sample, slice it extremely thin—thin enough that electrons can pass through it—and then shoot a beam of electrons at it. The electrons that make it through carry information about the sample's internal structure. Lenses magnify this information and project it onto a detector, producing an image.

The "extremely thin" part is crucial. Electrons don't penetrate matter the way X-rays do. If your sample is too thick, the electrons simply scatter in all directions or get absorbed entirely. For TEM to work, samples typically need to be less than a few hundred nanometers thick. That's thinner than a wavelength of visible light. Preparing such samples requires considerable skill, specialized equipment, and often the right touch of luck.

The second type is the scanning electron microscope, or SEM. This instrument takes an entirely different approach. Instead of shooting electrons through a sample, it bounces them off the surface. A tightly focused electron beam sweeps across the sample in a raster pattern—left to right, top to bottom, like an old television painting an image—and detectors measure the electrons that scatter back. By recording the intensity of these scattered electrons at each point, the microscope builds up an image of the sample's surface.

The results look strikingly different from TEM images. Because SEM captures surface information and uses geometric effects to create shadows, SEM images have a three-dimensional quality that feels almost tactile. The famous images of insect faces with compound eyes, pollen grains covered in intricate spikes, or the surface of a virus particle—these typically come from scanning electron microscopes.

There's also a hybrid approach called scanning transmission electron microscopy, or STEM, which combines features of both techniques. A focused beam scans across a thin sample, like in SEM, but the microscope primarily captures electrons that pass through, like in TEM. This approach enables certain analytical techniques that are difficult or impossible with either pure TEM or pure SEM.

How Deep Can We See?

For decades, a frustrating barrier limited what electron microscopes could resolve. The problem wasn't the wavelength of electrons—that was short enough to see individual atoms. The problem was the lenses.

Glass lenses, the kind used in optical microscopes, can be ground and polished to extraordinary precision. Electromagnetic lenses, which use magnetic fields to bend electron beams, are far harder to perfect. They suffer from a defect called spherical aberration: electrons passing through different parts of the lens get bent by slightly different amounts, blurring the final image. It's as if you were looking through a warped window. You can see something, but the fine details smear together.

For most of the twentieth century, there was no good solution to this problem. Physicists knew spherical aberration existed. They knew it was limiting their microscopes. But correcting it required adding additional magnetic elements whose fields would cancel out the aberration, and designing such correctors turned out to be devilishly difficult.

The breakthrough came in the late 1990s and early 2000s, when researchers finally developed practical aberration correctors. These are complex assemblies of magnetic multipoles—elements that produce precisely shaped magnetic fields—arranged to compensate for the distortions introduced by the main lenses. With aberration correction, the resolution of transmission electron microscopes improved dramatically, dropping below 0.5 angstroms. An angstrom is one ten-billionth of a meter. At this scale, individual atoms become clearly visible. You can map out the precise arrangement of atoms in a crystal lattice. You can see the atomic structure of the materials that make up computer chips, battery electrodes, or the protein coats of viruses.

Modern high-resolution electron microscopes can achieve magnifications exceeding fifty million times. To put that number in perspective: if you magnified a grain of sand fifty million times, it would appear larger than a house.

What Electrons Reveal

Electron microscopes don't just produce pretty pictures. They enable a remarkable variety of analytical techniques that reveal the composition and structure of matter at the atomic scale.

When high-energy electrons slam into a sample, they interact with its atoms in multiple ways. Some electrons bounce straight back. Some knock other electrons loose, generating what are called secondary electrons. Some cause the atoms to emit X-rays. Each of these signals carries different information.

Secondary electrons, the ones knocked loose from atoms near the sample surface, are particularly useful for imaging topography. These electrons have very low energies—around fifty electron volts—which means they can only escape from the top few nanometers of the sample. An electron that's generated any deeper simply doesn't have enough energy to make it out. This surface sensitivity is what gives scanning electron microscope images their remarkable three-dimensional appearance. Edges and steep surfaces appear bright because more secondary electrons can escape from them. Flat surfaces appear darker.

Backscattered electrons—the ones that bounce directly off atoms in the sample—reveal different information. Heavy atoms, the ones with many protons in their nuclei, backscatter electrons more efficiently than light atoms. This means areas of a sample containing heavy elements appear brighter in a backscattered electron image. Scientists use this to identify regions with different chemical compositions without needing to do any additional analysis.

X-ray emission provides even more specific chemical information. When a high-energy electron knocks an inner-shell electron out of an atom, an outer electron drops down to fill the vacancy. The energy difference gets released as an X-ray. And here's the key: the energy of that X-ray depends on which element the atom belongs to. Iron produces X-rays with one characteristic energy. Copper produces X-rays with a different energy. By measuring the energies of X-rays coming from a sample, scientists can determine exactly which elements are present and where they're located.

This technique, called X-ray microanalysis or energy-dispersive X-ray spectroscopy, has become indispensable for materials science, geology, semiconductor manufacturing, and countless other fields. You can scan an electron beam across a sample and build up a color-coded map showing the distribution of different elements—carbon in red, oxygen in blue, silicon in green. It's like having a chemical camera.

From Crystals to Vaccines

Electron microscopes transformed our understanding of the microscopic world, and few areas benefited more than biology and medicine.

Consider viruses. Before electron microscopes, scientists knew that viruses existed—they could demonstrate their effects, pass them through filters, show they caused disease—but no one had actually seen one. Viruses are simply too small for light microscopes. The first clear images of viruses came from electron microscopes in the late 1930s, revealing bizarre geometric shapes: icosahedrons, rods, complex structures with head-and-tail arrangements that looked like nothing else in biology.

Understanding viral structure became essential for understanding how viruses work and, eventually, for designing vaccines against them. The polio vaccine, developed in the 1950s, depended in part on electron microscopy studies that revealed the structure of the poliovirus. More recent vaccines, including those against coronaviruses, build on decades of electron microscopy research that mapped out viral surface proteins in atomic detail.

The technique called cryo-electron microscopy, which earned its developers the 2017 Nobel Prize in Chemistry, pushes this even further. By flash-freezing biological samples in vitreous ice—water that's cooled so rapidly it doesn't have time to form crystals—researchers can capture proteins and other biological molecules in their natural states. Computer algorithms then combine thousands or millions of individual images to reconstruct three-dimensional structures at near-atomic resolution. This approach has revolutionized structural biology, enabling scientists to determine the shapes of molecules that would be impossible to study using traditional methods like X-ray crystallography.

The Ongoing Revolution

Electron microscopy continues to advance. The development of direct electron detectors in the 2010s—sensors that detect electrons directly rather than converting them to light first—improved both sensitivity and resolution. Four-dimensional scanning transmission electron microscopy collects full diffraction patterns at each point in a scan, enabling new kinds of analysis. Environmental electron microscopes allow researchers to watch chemical reactions happen in real time, observing how materials change under different atmospheric conditions or temperatures.

The instruments have become more accessible too. While the most advanced aberration-corrected microscopes still cost millions of dollars and require specialized facilities, simpler electron microscopes have become routine equipment in university laboratories, hospitals, and industrial research centers around the world. What was once an exotic technology accessible only to a handful of specialists has become a standard tool of scientific investigation.

In a sense, the electron microscope represents one of humanity's great technological achievements: the extension of our senses into a realm that evolution never prepared us for. We evolved to perceive objects measured in meters, to respond to dangers we could see with our eyes. Atoms and molecules were, for most of human history, purely theoretical constructs. The electron microscope made them real. It let us see the building blocks of matter directly, opening up fields of investigation that have shaped everything from computer chips to cancer treatments to the vaccines that protect us from disease.

Ruska and Knoll built their first crude instrument in 1931 trying to understand electron beams. They could not have imagined that their work would one day let scientists watch individual atoms move, map the structure of viruses, and peer into the molecular machinery of life itself. That is the nature of fundamental research: you pull on one thread of curiosity, and sometimes you unravel an entirely new way of seeing the world.