“One thing I liked about being in microscopy is it gets you out of your box constantly because there’s such a diverse range of applications.“
Nobel prize laureate Eric Betzig brings it to the point: Looking at an actual process can make us learn a lot. Why is that so? This all goes back to the type of data you are looking at. Researchers have different tools to look at biological processes. Many of those methods include processing samples of biological material (meaning simply to smash up entire organs or cells they want to look at) to have enough to perform a measurement. Clearly this measurement will give scientists an average across for example all smashed up cells. But what if some cells behave different than others? You see were I am going. As with any kind of data, the average is an approximation of an tendency across all cells together, but the positional information and dynamics of an individual cell are lost. Imaging technologies and visualization of biological phenomena has thus been immensely powerful to unravel nature’s mysteries. These astonishing images are not only pretty but also revolutionize our understanding of our own bodies and minds.
It is not all about visualizing minuscule objects anymore. As early as in the 17th century, scientists used light microscopy to make micrometer scaled structures visible for the eye. Besides this now-a-days routine application of microscopes, a new challenge is to image large structures or entire organs. Why large structures? A great example is the brain, which harbors billions of nerve cells including different types of neurons. How individual neurons function and transmit information from one cell to the next has been largely understood. But to grasp how we think, behave and cognitive processes emerge still remains elusive. Cleary, looking at single cells does not answer the question of how the brain functions, as this is determined by the interaction and cooperation of many nerve cells. Scientists have turned to a new method, appropriately called CLARITY, to elucidate how brain cells are wired up. As with many annoying problems, fat is the issue. Cells are surrounded within a lipid membrane that obscure the view on the brain with a microscope. Stanford scientists found a way to preserve the structure of the brain, get rid of the fat and make tissues completely transparent to zoom in (to see how it is done and of course pretty images 🙂 check out the video)!
“CLARITY is powerful. It will enable researchers to study neurological diseases and disorders, focusing on diseased or damaged structures without losing a global perspective. That’s something we’ve never before been able to do in three dimensions.”
Francis Collins, Director of the National Institute of Health.
Imaging is entering the world of superlatives – Microscopes turning into Nanoscopes
Light microscopes face the limitation of the diffraction limit. Meaning conventional microscopes (they are still pretty fancy though) can depict two structures separately that are at least 200 nm apart from each other. Just to put this in perspective, 200nm are 0.2 millionths of a meter. Anything closer than this is represented as a fuzzy spot. For long, this was an excepted limit for imaging one’s favorite biological mystery. However, recently the field of super-resolution microscopy evolved. It means nothing less than the ability of a microscope to resolve structures beyond 200nm. So physics has been thrown over board? No, not really. Physics has actually been used to extend the resolution. For those interested in more details and physics-affine, watch this video on the iBiology platform.
For example, Clemens Kaminski from the University of Cambridge uses super-resolution microscopy to investigate how proteins are misshaped, like in diseases as Parkinson’s. But best let him explain it himself:
Eric Betzig, Stefan Hell and William Moerner received in 2014 the Noble Prize for extending the resolution power of microscope beyond the known limit.
Honey, I expanded the brain
A recent study, has explored an alternative strategy that might be easily applicable (meaning cheap) for many scientists. The core idea is to simply enlarge your object and then look at it. Expanding your sample of interest, like making a sponge swell by adding water, should defeat the diffraction limit. Yep simple, but apparently revolutionizing!
Source of header image Stanford Microscopy Facility