By combining quantum mechanical quirks of light with a technique called photonic force microscopy, scientists can now probe detailed structures inside living cells like never before. This ability could bring into focus previously invisible processes and help biologists better understand how cells work.
Photonic force microscopy is similar to atomic force microscopy, where a fine-tipped needle is used to scan the surface of something extremely small such as DNA. Rather than a needle, researchers used extremely tiny fat granules about 300 nanometers in diameter to map out the flow of cytoplasm inside yeast cells with high precision.
To see where these miniscule fat particles were, they shined a laser on them. Here, the researchers had to rely on what’s known as squeezed light. Photons of light are inherently noisy and because of this, a laser beam’s light particles won’t all hit a detector at the same time. There is a slight randomness to their arrival that makes for a fuzzy picture. But squeezed light uses quantum mechanical tricks to reduce this noise and clear up the fuzziness.
“The essential idea was to use this noise-reduced light to locate the nano-particles inside a cell,” said physicist Warwick Bowen of the University of Queensland in Australia, co-author of a paper that came out Feb. 4 in Physical Review X.
The reason behind all this was to overcome a fundamental optical limit that has always caused headaches for biologists. The diffraction limit of light puts a constraint on the size of something you can resolve with a microscope for a given wavelength of light. For visible wavelengths, this limit is about 250 nanometers. Anything smaller can’t be easily seen. The trouble is, a lot of structures inside of cells, including organelles, cytoskeletons, and individual proteins, are much smaller than this.
Scientists have come up with clever ways to get around the diffraction limit and resolve things as small as 20 nanometers. But the new quantum technique has pushed that limit even farther. Instead of using light, Bowen’s team passed a nano-particle over the surface of cellular structures, sort of like running your finger over a bumpy surface. They held onto their fat granule probe using optical tweezers, which are basically a nanoscale version of a tractor beam. In an optical tweezer, scientists create a laser beam with an electromagnetic field along its length. The field is strongest at the center of the beam, allowing tiny objects to be drawn to this point and held there.
Because the fat granules occur naturally, the cells don’t need to be prepared like they would for atomic force microscopy, which generally involves killing the cells. That’s a big deal because it means photonic force microscopy can be used to visualize processes inside living cells. The team has tracked these granules with a resolution of about 10 nanometers.