Bringing Quantum Microscopy to Biological Imaging

Physicists from the University of Glasgow and Heriot-Watt University have brought an exciting new dynamic to microscopic imaging having found a new way to harness Hong-Ou-Mandel (HOM)) interference, a quantum effect which has potential to drive advanced forms of microscopy for use in medical research and diagnostics. 

The team, led by Professor Daniele Faccio of Glasgow’s School of Physics and Astronomy, have used single-photon sensitive cameras to measure bunched and anti-bunched photons(1) to resolve microscopic images of some clear acrylic sprayed onto a microscope slide with an average depth of 13 microns and a set of letters spelling ‘UofG’ etched onto a piece of glass at around 8 microns deep. 

The results obtained demonstrated the possibilities of this approach as an alternative imaging method as Professor Faccio explains: “Conventional microscopy using visible light has taught us a vast amount about the natural world and helped us make an incredible array of technological advances.

“However, it does have some limitations which can be overcome by using quantum light to probe the microscopic realm. In bioimaging, where cells can be almost entirely transparent, being able to examine their fine details without using conventional light could be a major advantage – we chose to image transparent surfaces in this research precisely to demonstrate that potential.  

“Similarly, samples in conventional microscopes need to be kept perfectly still – introducing even a small vibration could introduce a level of blur which would ruin an image. However, HOM interference requires only measuring photon correlations and there is much less need for stability.” 

Having worked on HOM interference largely as a tool for sensing during the last decade, it was the Glasgow-based research team’s growing interest in imaging techniques that led to the current collaborative partnership.

“Several years ago we started to get very interested in imaging and computational imaging techniques and then realised that no-one had applied this approach to imaging with an actual camera. So we tried this out. It did take a while. I think all said and done, it took us a couple of years to get this right,” said Professor Faccio.

While the Glasgow –based team worked on the technical challenges of obtaining the bunching and anti-bunching information in the lab, the Heriot-Watt team provided the theory support: “They devised a method of using both the bunching and anti-bunching information to get images with lower noise (better quality images),” added Professor Faccio.

The team is currently progressing research using other materials, aiming to demonstrate that this technique can be used for actual microscopy and felt confident that results of biological imaging would be forthcoming.

“Now that we’ve established that it’s possible to build this kind of quantum microscopy by harnessing the Hong-Ou-Mandel effect, we’re keen to improve the technique to make it possible to resolve nanoscale images. It will require some clever engineering to achieve, but the prospect of being able to clearly see extremely small features like cell membranes or even strands of DNA is an exciting one.”

Expanding further Professor Faccio added: “We think there is space for significant improvement in terms of acquisition speed and resolution. The next steps will require better or different photon sources. The same is true also for the sensors and cameras. There are some interesting developments in the SPAD camera area that we want to exploit. This is where we will be pulling in additional expertise.”

While his own research team will be focusing on bio-imaging he believed that depth profiling and other industrial applications might find use of these approaches: “We will be reaching out to industry partners. We believe that the technique shown in the paper can be developed into a competitive imaging technology. There are some points to be addressed, including imaging speed, but we think we know how to do this,” Professor Faccio said.

The research was supported by funding from the Engineering and Physical Sciences Research Council, the European Union’s Horizon 2020 programme, the Royal Academy of Engineering and the Marie Sklodowska-Curie grant programme.

(1) Named after the three researchers who first demonstrated it in 1987, HOM interference occurs when quantum-entangled photons are passed through a beam splitter – a glass prism which can turn a single beam of light into two separate beams as it passes through. Inside the prism, the photons can either be reflected internally or transmitted outwards. 

When the photons are identical, they will always exit the splitter in the same direction, a process known as ‘bunching’. When the entangled photons are measured using photodetectors at the end of the path of the split beam of light, a characteristic ‘dip’ in the output probability graph of the light shows that the bunched photons are reaching only one detector and not the other. 

That dip is the Hong-Ou-Mandel effect, which demonstrates the perfect entanglement of two photons. It has been put to use in applications like logic gates in quantum computers, which require perfect entanglement in order to work. 

It has also been used in quantum sensing by putting a transparent surface between one output of the beam splitter and the photodetector, introducing a very slight delay into the time it takes for photons to be detected. Sophisticated analysis of the delay can help reconstruct details like the thickness of surfaces.

Now, the Glasgow-led team has applied it to microscopy, using single-photon sensitive cameras to measure the bunched and anti-bunched photons and resolve microscopic images of surfaces.

‘Quantum microscopy based on Hong-Ou-Mandel interference’, published in Nature Photonics. 

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