Chemists, biologists, clinicians, physicists and engineers rely on the capa­bilities of different types of microscopes to unveil the inner structures of organisms and matter that we cannot see with our naked eye. Most microscopes use light as the tool to illu­minate transparent or semi-trans­parent samples, and allow us to see what is happening inside. Some samples tolerate high intensity levels of light, but others, like some molecules and cells, are extremely delicate and become damaged or even die under such intense radiation. This is not good for experi­mental accuracy. To avoid hurting the samples, the best option would be to reduce the intensity of light.

But in doing so, the image becomes noisy and unsharp, which can obscure critical details in the image that provide important sample information to the observer. In trying to overcome this major barrier in micro­scopy, many studies have been searching for techniques that allow the imaging of very small, very sensitive samples, without actually modifying or damaging them in the process. One promising option nowadays is to use quantum light. Since 2018, the European project Q-mic has been working to develop quantum imaging for micro­scopy of very sensitive samples.

The team of researchers, which include ICFO researchers Robin Camphausen, Alvaro Cuevas, Luc Duempelmann, Roland Terborg, Ewelina Wajs, led by Valerio Pruneri, in colla­boration with the project partners Simone Tisa and Alessandro Ruggeri from Micro Photon Devices (MPD), Iris Cusini, from Politecnico di Milano and Fabian Stein­lechner, from Fraunhofer IOF, have reported on the results obtained from the new quantum-enhanced microscope that the whole consortium has developed. They report on the capabilities of this device in using very low intensity levels of light to image large areas of samples, with a higher sensi­tivity and reso­lution, compared to classical microscopes.

As Robin Camphausen explains, “the Q-MIC micro­scope is unique in the sense that it has been designed to actually illu­minate the sample using a special type of light, a “quantum light”. Instead of normal light, where many unordered photons reach the sample, the quantum source developed by the team uses pairs of entangled photons and sends them in small numbers to hit the sample and retrieve information in a more detailed and specific way.” Generally, using low levels of light to avoid damage unfortunately increases the amount of background noise in the measurement and hampers all details and sharpness you can get in the image. “It´s just like when the first mobile phones were launched into market. If you tried taking a picture at night with your friends, the sharpness of the picture was really bad because not enough photons would be captured to form a clear image so the pixels would look undefined, and also the background lights disturbed the quality of the image” clarifies Camp­hausen.

This issue is bypassed with this microscope, because it uses inter­ference patterns of entangled photons to actually reconstruct the image of the sample. Specifically, it integrates a quantum source, that generates space-polari­zation hyper-entangled photons, a large field of view lens free inter­ference microscope and a single photon avalanche diode (SPAD) array camera. “The device we built and the technique we developed actually uses the entanglement of photons to enhance the interference patterns obtained in the imaging process, and because of this quantum effect, we are able to reduce the noise level and increase the sensitivity of the measure­ments by more than 25 % when compared to classical measure­ments” comments Alvaro Cuevas.

In doing so, what the camera registers are not optical intensities nor single photon counts, but actually two-photon coinci­dences across the entire field of view. When the pairs of photons go through the device, a set of Savart plates divides them into two paths, and guides them to the sample. If the sample is flat, the path of the photons will be the same, but if the sample has different thick­nesses, the individual paths of the photons change and an inter­ference pattern is created on the detector. By repeating this process of sending in photons, the researchers obtain an inter­ference pattern image without the need of a pixel-to-pixel scanning system. And with the help of mathe­matical algorithms, they can reconstruct the image to find more details in the sample itself.

To confirm such improvement in the results, the researchers took a standard diag­nostic solution made of a sample of Protein A, used as a cali­bration tool. The proteins were deposited onto a glass slide, equally spaced out, and then the sample was mounted on a sample holder inside the microscope. Firstly, the sample was initially illu­minated with classical light and then with quantum light; secondly, the respective inter­ference patterns were obtained, and, finally, the images recon­structed. What they saw is that the quantum technique retrieves a much smoother image when compared to the classical one.

Even though the quantum image was recon­structed using fewer photons than the classical one, the smoothness of the image was much cleaner. Cuevas summarizes this as follows, “when we refer to smoothness, it means that if you take an image of a flat surface with low intensity classical light, the level of noise seen in the image is due to the randomness in the level of the data, basically the noise that comes from all the discrete disor­dered photons that constitute this type of light. With quantum light, the noise level and thus the randomness is reduced, so you get better infor­mation about sharp edges, which, in the end, is essential for recognizing concen­trations, depths, heights of the samples”.

The results are very promising and enable a completely new way of imple­menting quantum imaging in everyday sensing and imaging technology. As Valerio Pruneri, coor­dinator of the project, finally emphasizes, “this innovative device has the potential to become an everyday tool used at large… it shows amazing capabilities that can definitely be exploited in several appli­cations, ranging from material sciences, analysing trans­parent surfaces for quality assurance in flexible electronics, to quantum cryptography for secure communi­cations or ultra-sensitive imaging of micro-organisms, viruses, and molecules, just to mention a few.” (Source: ICFO)

Reference: R. Camphausen et al.: A quantum-enhanced wide-field phase imager, Sci. Adv. 7, abj2155 (2021); DOI: 10.1126/sciadv.abj2155

Link: Optoelectronics, ICFO-Institut de Ciencies Fotoniques, Barcelona, Spain