The Nobel Prize, microscopy, and nanoscopy

The entrance to the Nobel Museum in Stockholm, Sweden.

The entrance to the Nobel Museum in Stockholm, Sweden.
(http://www.nobelmuseum.se/en/exhibitions/
cultures-of-creativity
)

Nobel Prizes in the sciences are awarded for significant achievements and discoveries that have held up over time. The Nobel Museum in Stockholm, Sweden, does a wonderful job of explaining the science behind those prizes and their impact, but you don’t have to go to Stockholm to learn about one recent award. Instead, you can go to The Corning Museum of Glass in Corning, N.Y., to see the exhibition Revealing the Invisible: The History of Glass and the Microscope. But hurry — the exhibition closes Sunday, March 19!

It seems that everywhere we look these days, we see topics related to very tiny worlds, sometimes called nanoworlds. The word “nano” means one billionth, versus “micro” meaning one millionth. The ordinary world is one million times bigger than the microworld, and the microworld is still 1,000 times bigger than the nanoworld. The cutting-edge microscopes of the past have given way to today’s nanoscopes that can see viruses, proteins, and even nanomolecules.

Comparison of scales, ranging from the “ordinary” world we live in down to the “microworld” and the “nanoworld.”

Comparison of scales, ranging from the “ordinary” world
we live in down to the “microworld” and the “nanoworld.”
(https://www.emaze.com/@ACWWTOQC/
Presentation-Name
)

Three ways to describe the limitation on our ability to distinguish between two different light sources.

Three ways to describe the limitation on our ability to
distinguish between two different light sources.
From http://advanced-microscopy.utah.edu/education/
super-res/

 

The 1800s were a golden age for optical microscopes, with improvements that led to an avalanche of discoveries about cells and bacteria, improving public health in ways that saved countless lives. The near perfection of the optical microscope coincided with the invention of scientific glass by Schott, Abbe, and Zeiss (read an article about them at https://www.cmog.org/article/microscopes) and the discouraging discovery that there is a limit to the details that an optical microscope can provide. This limitation is still described as the Abbe limit.

Makers of 20th-century optical microscopes addressed this limitation in several creative ways. In 1903, Richard Zsigmondy’s ultramicroscope (Nobel Prize in Chemistry, 1925) used light scattering rather than light reflection. Fritz Zernike’s phase contrast microscope (1930s) shined light through living cells, converting invisible phase shifts into variations in brightness (Nobel Prize in Physics, 1953). Ernst Ruska’s invention of the electron microscope (1938) took resolution even further beyond the Abbe limit, but its electron beams destroyed living tissues. Other creative imaging techniques also used methods not involving light, but still could not always determine desired details of small regions in living beings.

A decade ago, Stefan Hell (German, b. 1962), William Moerner (American, b. 1953), and Eric Betzig (American, b. 1960) figured out two new methods for defeating the Abbe limit and for creating the most detailed images ever produced of biological molecules and processes. Their methods make molecules fluoresce, just as ultraviolet light makes fluorescent paints glow.

In Hell’s method, one laser sets a region of molecules aglow; another laser cancels the resulting light except for light coming from a tiny zone. Joining images from those zones produces a picture of any region desired.

Improved resolution provided by Dr. Hell’s method.

Improved resolution provided by Dr. Hell’s method. http://www.mpibpc.mpg.de/hell

These images all show the same lysosome membranes. Left, an image made via conventional microscopy. Center, an early image made by Betzig using his new method. Right, an enlarged version, with the scale marking of 0.2 microns indicating the Abbe limit. From Science 313: 1642–1645.

These images all show the same lysosome membranes. Left, an image made via conventional microscopy. Center, an early image made by Betzig using his new method. Right, an enlarged version, with the scale marking of 0.2 microns indicating the Abbe limit. From Science 313: 1642–1645.

The second method, developed by Betzig and Moerner, makes one single molecule glow, using a protein isolated in sea jellies. Combining images of individual molecules yields a highly detailed image. In 2014, these three scientists received the Nobel Prize in Chemistry for this work.

Microscopy at this scale is called nanoscopy. Just as earlier optical microscopy advanced medical practice by enabling the study of cells and bacteria, nanoscopy promises further understanding of viruses and proteins, a development of great potential for humankind.


Micrographia (London, 1665), Robert Hooke.

Revealing the Invisible: The History of Glass and the Microscope is open 9 am to 5 pm every day through March 19, 2017. This exhibition tells the stories of scientists’ and artists’ exploration of the microscopic world between the 1600s and the late 1800s. Unleash your sense of discovery as you explore the invisible through historic microscopes, rare books, and period illustrations, and take a #cellfie in the Be Microscopic interactive.

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