Defying the Limits of the Visible
(June 1st, 2017) Viruses, proteins or subcellular structures are only possible to observe through expensive techniques that often kill or destroy the sample. But this might change as a group of scientists in Europe are pushing the boundaries of what optics has so far allowed us.
How far into the microworld can we go by developing instruments that amplify what is invisible to the naked eye? Is there a limit? In the nineteenth century, German physicist Ernst Abbe built a theoretical framework to answer this question. His work showed that, as long as our magnifying devices depend on light, we would not be able to distinguish two points that are closer than half the wavelength of the light used. This translates as not being able to go below 200nm, approximately.
This phenomenon, known as the diffraction limit, is described by an equation that was engraved in Jena, Germany, in a memorial dedicated to Abbe. Although it is literally carved in stone, it has not stopped scientists trying to go beyond. For instance, the electron microscope does not rely on light but on electrons (having those much shorter wavelengths). The disadvantage of this technique is, however, that it cannot handle sensitive living samples and that it is a very expensive technique, both in terms of time and money.
Starting this year, a group of scientists, funded by the European Union, is facing the diffraction limit with a different approach. The initiative is called “ChipScope” and the goal is to build an optical microscope as small as a chip, with super-resolution capacity and without some of the disadvantages of electron microscopy.
“The current problem is that the shortest wavelength of visible light is about 400nm. The intention of the project is to develop LEDs (Light-Emitting Diodes) of 50nm,” says Angel Dieguez, professor at the University of Barcelona and coordinator of the ChipScope project. He further explains that the idea is to build a two-dimensional array of 64 x 64 nano-LEDs, nanometrically spaced, where “each of them would switch on one after the other, forming the image of the object”. Dieguez points out that “this image is not built as in a traditional camera”. There will be a photodetector that receives the signal of each nano-LED in time and space, and will return a 1 or a 0, “so instead of having an analogue representation, we will have digital information that will be translated into the image we want to observe”. The idea sounds promising but could still take a while before it's realised. Even today, the smallest LEDs available are above one thousand nanometres.
Chipscope, scheduled to run until December 2020, has secured a funding of €3.75 million. But convincing the EU officials took some time. Dieguez comments that they have submitted four applications since the end of 2014. All in all, seven partners from five European countries are involved: the University of Barcelona (Spain), the Braunschweig University of Technology (Germany), the Austrian Institute of Technology (Austria), the University of Rome (Italy), the company Expert Ymaging SL (Spain), the Swiss Foundation for Research in Microtechnology (Switzerland) and the Medical University of Vienna (Austria), each of them bringing different knowledge, expertise and technology to the table.
It is the seventh partner, a research group investigating a pulmonary disease at the Medical University of Vienna, which will perform the first practical tests with the microscope. If ChipScope accomplishes its goal, this technology might, for instance, help visualising subcellular structures in living cells that, so far, have only been observed in dead and highly manipulated samples with electron microscopy.
But the ambition is not restricted to building a microscope used in sophisticated advanced research. “The idea is also to make a portable chip-sized microscope that can be used in daily applications,” says Dieguez. He comments that such a device could be really cheap, with a price on the order of 100 euros. It could also be improved to get images with better quality but the cost would still be much lower than for super high-resolution devices, currently on the market.
From routine applications to high-level, perhaps even clinical research, ChipScope could revolutionise imaging in the life sciences and beyond. It's also another example of how science, continuously, pushes limits and reveals what was unimaginable before.