A team of researchers in Germany and Australia recently used a new microscopy technique to image nano-scale biological structures at a previously unmanageable resolution, without destroying the living cell. The technique, which employs laser light many millions of times brighter than the Sun, has implications for biomedical and navigation technologies.
The quantum optical microscope is an example of how the strange principle of quantum entanglement can feature in real-world applications. Two particles are entangled when their properties are interdependent—by measuring one of them, you can also know the properties of the other.
The sensor in the team’s microscope, described in a paper published today in Science, hinges on quantum light—entangled pairs of photons—to see better-resolved structures without damaging them.
“The key question we answer is whether quantum light can allow performance in microscopes that goes beyond the limits of what is possible using conventional techniques,” said Warwick Bowen, a quantum physicist at the University of Queensland in Australia and co-author of the new study, in an email. Bowen’s team found that, in fact, it can. “We demonstrate [that] for the first time, showing that quantum correlations can allow performance (improved contrast/clarity) beyond the limit due to photodamage in regular microscopes.” By photodamage, Bowen is referring to the way a laser bombardment of photons can degrade or destroy a microscope’s target, similar to the way ants will get crispy under a magnifying glass.
Microscopes have allowed humans to understand biology on a deeper level since the 16th century, and today’s advanced microscopes are so much more than a couple aligned lenses. Innovations like scanning tunneling microscopes, for example, can see individual atoms. In the new work, the researchers shone powerful laser light onto a yeast cell to reveal the intricacies of its substructures. They were able to get the higher resolution they wanted thanks to the entangled photons, since “detecting one photon gives you information about when the next photon will arrive,” Bowen explained.
“This experiment is a beautiful example on how quantum techniques are now being harnessed towards a better understanding of biological processes,” said Clarice Aiello, a quantum engineer specializing in nanoscale biophysics at UCLA who is not affiliated with the recent paper. “Technical hurdles ... will need to be overcome before the technology becomes commercial, but this experiment is a proof-of-principle that quantum techniques developed decades ago can and will be deployed to great advantage in the life sciences.”
While other microscopes operating with such intense light end up sizzling holes in what they’re trying to study, the team’s method didn’t. The researchers chemically fingerprinted a yeast cell using Raman scattering, which observes how some photons scatter off a given molecule to understand that molecule’s vibrational signature. Raman microscopes are often used for this sort of fingerprinting, but the whole destroying-the-thing-we’re-trying-to-observe has long vexed researchers trying to see in higher resolutions. In this case, the team could see the cell’s lipid concentrations by using correlated photon pairs to get a great view of the cell without increasing the intensity of the microscope’s laser beam.
Charles Camp, an electrical engineer at the National Institute of Standards and Technology who specializes in Raman imaging, said in an email that Raman methods “have long promised to revolutionize biological imaging” but have had various limitations. But in the new study, the researchers “present a proof-of-principle system and relatively practical way forward to enhancing [stimulated Raman scattering] microscopy,” Camp said.
“We were able to clearly resolve the cell wall, which is a few-nanometers-thick structure that (of course) surrounds the cell,” Bowen said. “With other Raman microscopes, it is very difficult to resolve the cell wall, and we showed in our case that our microscope could only very faintly see this without quantum correlations.”
Depending on who you are, it’s either terrifying or strangely comforting to think about how we are all just a sum of cells, forged together on micro-scales to form limbs and internal organs and all the complex systems that make us tick. But zoom in even further, and there are even smaller biological structures yet to be fully understood. Impressive new imaging techniques are allowing us to squint a little harder at this utterly unfamiliar realm.
This article has been updated with comments from Clarice Aiello and Charles Camp.