Light microscopes are limited in their ability to see viruses due to their small size, which is typically around 150 nanometers[1][5]. However, recent advances in light microscopy have allowed for the visualization of virus particles using techniques such as fluorescence microscopy and Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) [1][4][5]. These techniques allow for the detection and analysis of individual virus particles, although they may not provide the same level of detail as electron microscopy[1][3].
Electron microscopes are used to visualize viruses because their size is below the limit of resolution of light microscopes. Viruses are about 1,000 times smaller than most cells, with an average size of around 150 nanometers, which is below the resolution of light microscopes that can only show objects larger than half the wavelength of visible light. Electron microscopy, particularly transmission electron microscopy (TEM), has made a major contribution to virology by allowing the visualization of viruses, as electrons have a much shorter wavelength than visible light, enabling the imaging of smaller objects. This technique has been valuable in the surveillance of emerging diseases and potential bioterrorism, as well as in the discovery and description of viruses[7][8][9]. Therefore, the small size of viruses is the reason why they cannot be seen with traditional light microscopes.
What About Big Viruses?
Yes, some of the largest viruses, such as Mimivirus, can be visualized with light microscopes. Mimivirus is the largest virus ever discovered, with a diameter of 750 nanometers and a genome of 1.2 million base pairs[14]. It was initially mistaken for a bacterium due to its large size and ability to form visible plaques[14].
Giant viruses, like Mimivirus, are visible under a light microscope because of their large size, which disrupts diffusion and the formation of visible plaques[14]. This feature makes them suitable for teaching materials in biology courses, as they can be easily observed and studied under a light microscope[15].
In addition to light microscopy, other imaging techniques, such as transmission electron microscopy (TEM) and scanning electron microscopy (SEM), have been used to study giant viruses[12][13]. These methods provide more detailed information about the structure and morphology of these large viruses.
Why is There a Limit for Light Microscopes?
Light travels as packets of waves and the wavelengths of these determines the colors we see when the reach the receptors in our eyes. When light hits something, some wavelengths are absorbed and some are reflected. Occasionally an object is excited by the light that hits and gives off light of its own (it glows rather than just reflecting light). At a very a very small scale, there are limits to light microscope images because light can’t hit and be reflected by things that are too small. You can think of it as the packet of light waving right around the small stuff. The light might even move a very small particle instead of bouncing off of it. Microscopes can not see most viruses for this reason.
An ordinary light microscope uses photons of light, which are equivalent to waves with a wavelength of roughly 400–700 nanometers. That’s fine for studying something like a human hair, which is about 100 times bigger (50,000–100,000 nanometers in diameter). But what about a bacteria that’s 200 nanometers across or a protein just 10 nanometers long? If you want to see finely detailed things that are “smaller than light” (smaller than the wavelength of photons), you need to use particles that have an even shorter wavelength than photons: in other words, you need to use electrons. (ExplainThatStuff)
Electron microscopes use a beam of electrons instead of light. They require samples to be killed and fixed in place in a vacuum chamber because electrons don’t travel far in air. There are a few different kinds of electron microscopes, but some of the best images of viruses come from scanning electron microscopes. SEMs shoot a beam of electrons (guided by electro magnets) across the surface of the sample and detectors use the reflected electrons to build a 3D picture. They can only see things about 10 nanometers in size, but the SARS-CoV-2 virus, for example, is about 120 nm across. Although SEMs are typically about 10 times less powerful than another common type of electron microscope, they produce very sharp, 3D images (compared to flat images produced by TEMs), plus their specimens need less preparation.
Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923496/
[2] https://youtube.com/watch?v=45lJyeCp9SY
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772359/
[4] https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0179728
[5] https://theconversation.com/five-techniques-were-using-to-uncover-the-secrets-of-viruses-144363
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772359/
[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161876/
[8] https://theconversation.com/five-techniques-were-using-to-uncover-the-secrets-of-viruses-144363
[9] https://onlinelibrary.wiley.com/doi/pdf/10.1042/BC20070173
[10] https://physics.stackexchange.com/questions/546159/why-viruses-cannot-be-seen
[11] https://www.sciencedirect.com/science/article/pii/S1369527416000023
[12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332949/
[13] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197374/
[14] https://www.americanscientist.org/article/giant-viruses
[15] https://iubmb.onlinelibrary.wiley.com/doi/am-pdf/10.1002/bmb.21249
