Nobel Prize 2014: Super-resolved fluorescence microscopy

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2014 to

Eric Betzig

Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA,

Stefan W. Hell

Max Planck Institute for Biophysical Chemistry, Göttingen, and German Cancer Research Center, Heidelberg, Germany

and

William E. Moerner

Stanford University, Stanford, CA, USA

“for the development of
super-resolved fluorescence microscopy”

Surpassing the limitations of the light microscope

For a long time optical microscopy was held back by a presumed limitation: that it would never obtain a better resolution than half the wavelength of light. Helped by fluorescent molecules the Nobel Laureates in Chemistry 2014 ingeniously circumvented this limitation. Their ground-breaking work has brought optical microscopy into the nanodimension.

In what has become known as nanoscopy, scientists visualize the pathways of individual molecules inside living cells. They can see how molecules create synapses between nerve cells in the brain; they can track proteins involved in Parkinson’s, Alzheimer’s and Huntington’s diseases as they aggregate; they follow individual proteins in fertilized eggs as these divide into embryos.

It was all but obvious that scientists should ever be able to study living cells in the tiniest molecular detail. In 1873, the microscopist Ernst Abbe stipulated a physical limit for the maximum resolution of traditional optical microscopy: it could never become better than 0.2 micrometres. Eric Betzig, Stefan W. Hell and William E. Moerner are awarded the Nobel Prize in Chemistry 2014 for having bypassed this limit. Due to their achievements the optical microscope can now peer into the nanoworld.

Two separate principles are rewarded. 

One enables the method stimulated emission depletion (STED) microscopy, developed by Stefan Hell in 2000. Two laser beams are utilized; one stimulates fluorescent molecules to glow, another cancels out all fluorescence except for that in a nanometre-sized volume. Scanning over the sample, nanometre for nanometre, yields an image with a resolution better than Abbe’s stipulated limit.

Eric Betzig and William Moerner, working separately, laid the foundation for the second method, single-molecule microscopy. The method relies upon the possibility to turn the fluorescence of individual molecules on and off. Scientists image the same area multiple times, letting just a few interspersed molecules glow each time. Superimposing these images yields a dense super-image resolved at the nanolevel. In 2006 Eric Betzig utilized this method for the first time.

Today, nanoscopy is used world-wide and new knowledge of greatest benefit to mankind is produced on a daily basis.

This video is a brief animation of how STED works and how it improves resolution of individual particles.

This video is a longer, more detailed presentation by one of the Nobel laureates (Hell).

What can we use from this in teaching undergraduate A&P?

• Discuss how this technology has enabled us to better visualize the chemicals and structures within our cells, enabling scientists to better understand the structure and function of cell, organelles, microbiome constituents, and other structures of the human body.


• If you do a brief run-through of the theory of microscopy—perhaps in your A&P lab—you can add a mention of this technology.  


• Your textbook or other learning resource may already have an example of this type of microscopy.


• A discussion of this  Nobel Prize could evolve into a meaningful example of how science works, including how incremental improvements in classical tools for observation expand the number of questions that can be answered.


• Use the links below (and images above) to use for a handout and/or teaching slides.

Want to know more?

Resources from Nobelprize.org

• Popular Information 
• Handout: Overview information in plain English
• my-ap.us/1rh0fAJ
• Scientific Background
• Handout: More detailed information includes references to original research articles
• my-ap.us/ZdLJ69
• Advanced Information
• Handout
• my-ap.us/1rh0dsp
• Images
• Can be used in your course
• Abbe's diffraction limit
• my-ap.us/ZR0LA8
• The principle of STED microscopy
• my-ap.us/1ncRH2C
• The principle of single-molecule microscopy
• my-ap.us/1pQbAZ4
• Biographies
• Eric Betzig, 
• U.S. citizen. Born 1960 in Ann Arbor, MI, USA. Ph.D. 1988 from Cornell University, Ithaca, NY, USA. Group Leader at Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
• http://janelia.org/lab/betzig-lab
• Stefan W. Hell, German citizen. 
• Born 1962 in Arad, Romania. Ph.D. 1990 from the University of Heidelberg, Germany. Director at the Max Planck Institute for Biophysical Chemistry, Göttingen, and Division head at the German Cancer Research Center, Heidelberg, Germany.
• http://www3.mpibpc.mpg.de/groups/hell
• William E. Moerner, U.S. citizen. 
• Born 1953 in Pleasanton, CA, USA. Ph.D. 1982 from Cornell University, Ithaca, NY, USA. Harry S. Mosher Professor in Chemistry and Professor, by courtesy, of Applied Physics at Stanford University, Stanford, CA, USA.
• http://web.stanford.edu/group/moerner

Diagrram cretit: Ganbaatar

Micrograph credit: Tesselkaffee

Text adapted from press release from Nobel Media