Breaking the Diffraction Limit

The human eye is limited: we can only see objects that are at least .1 millimeters wide. However, many of the cells that scientists work with are much smaller than that, often ten thousand times smaller than .1 millimeters. To solve this problem, we invented the microscope: lo and behold! —we could see single cells! With our new pictures, we understood that cells are the basic building block of all life. Soon, however, we realized that there were things smaller than the cells like organelles, viruses, and DNA. The most naive assumption was to increase the power of the microscope, but we soon reached another obstacle — the diffraction limit. Microscopes could only zoom in so much, and we were now in need of another visualization device. Scientists worked long and hard to find a solution to this problem. One discovery, the electron microscope, provided a temporary solution, but it could only analyze dead creatures. Another discovery was the use of fluorescent proteins that could attach to certain parts of a cell, allowing scientists to see the rough shape of the interior of a cell through the fluorescent glow. While this expanded the range of things we could see, it wasn’t perfect. It's kind of like looking at a city’s lights at night from a plane and trying to distinguish its exact shape. Slowly, groups of engineers and scientists began to fine-tune the idea of fluorescence. The biggest breakthrough happened in 2014 and made use of the concept of layered imaging. The main problem with fluorescence is that the cells were 3-D objects. So fluorescing molecules from the bottom of the cell interfered with those on the top of the cell, creating a lot of background noise. The new microscope, therefore, would only look at one “layer” of the cell at a time, nearly eliminating all background noise. Using this new technology, we have seen the working brain of a fly, working macrophages, and more, which has opened up hundreds of new questions to answer. For giving us a new vision, the microscope won Nobel prize in 2014.