The microscope was created over 350 years ago and considered a pioneering discovery at the time. Today it is ubiquitous in many fields of science: chemists, biologists, clinicians, physicists and even engineers use them to discover the inner structures of organisms and matter that we cannot see with the naked eye.

Most use light as their main tool to illuminate transparent or semi-transparent samples and see what’s going on inside them. While some samples are able to tolerate high levels of light radiation, others (such as some molecules and cells) are extremely delicate and are damaged or even killed by high light, creating problems when conducting high-precision experiments.

Some molecules and cells are extremely delicate and are damaged or even die under intense light radiation.

To avoid this, the best option is to reduce the light intensity, but when you do this, the image tends to become noisy and unclear, which can obscure critical details that can provide crucial information for the viewer.

To overcome this barrier in microscopy, techniques that allow obtaining images of very small and sensitive samples, but without modifying or damaging them in the process, have been sought. A very promising option is to use quantum light.

Quantum Microscopy

Since 2018, the European project Q-mic focuses on this line of research through quantum microscopy. The results of the work, specifically the new improved quantum microscope that the consortium developed, were published in the journal. Advances in Science. The authors belong to the Institute of Photonic Sciences (ICFO) and centers in Italy and Germany.

The study demonstrates the capabilities of this device, which uses extremely low-intensity quantum light, to obtain images of samples with a wide field of view, with greater sensitivity and resolution, compared to the classic microscopes currently used.

Very low intensity quantum light allows images with higher sensitivity and resolution

“The Q-MIC microscope is unique in that it is designed to illuminate the sample with a special type of light, a ‘quantum light.’ Instead of normal light, where many disordered photons hit the sample, the quantum source developed by our team uses entangled photon pairs and sends them out in small amounts to impact the sample and retrieve information in a more detailed and specific way”, says Robin Camphausen of the ICFO.

In general, the light of very low intensity is used mainly to avoid any permanent damage to the sample, but unfortunately this generates an increase in the amount of background noise in the measurement and tends to hide and distort all the details and sharpness of the image.

“It’s like when the first cell phones hit the market. If you were trying to take a picture at night with your friends, the image sharpness was very poor because not enough photons were captured to form a sharp image, so the pixels looked fuzzy and also the backlights hindered the image quality. the photo”, explains the researcher.

Our microscope uses entangled pairs of photons and sends them out in small amounts to impact the sample and retrieve information in a more detailed and specific way.

Robin Camphausen

However, this microscope uses entangled photon interference patterns to reconstruct the sample image. “The device we built and the technique we developed actually uses this photon entanglement to improve the interference patterns obtained in the imaging process and, because of this quantum effect, we can reduce the noise level and increase the sensitivity of measurements by more than 25% in relation to the classic measures”, comments Álvaro Cuevas, also from ICFO and co-author of the article.

What the camera records are not optical intensity levels or individual photon events, but coincidences of two photons across the entire field of view. When pairs of photons pass through the device, a set of Savart plates (crystals used to split a beam of light into two beams with different polarizations, one horizontal and one vertical) splits them into two paths and guides them towards the sample. .

If the sample is flat, the photon path will be the same, but if the sample has different thicknesses, the individual photon paths change and an interference pattern is created in the detector. By repeating this process, researchers obtain an image of this pattern without the need to use a pixel-by-pixel counting and scanning system. With the help of mathematical algorithms, they can reconstruct the image to find more details in the sample itself.

A sample of protein A

To verify an improvement in the image, the researchers collected a sample of protein A, which is a typical standard diagnostic solution used as a calibration tool.

Proteins were seeded onto cells on a glass slide, evenly spaced and then mounted on a slide under the microscope. First, the sample was illuminated with classical light and then with quantum light. Then, the respective interference patterns were obtained and, finally, the images were reconstructed. The team noted that the quantum light technique recovers a much smoother image compared to the classical one.

Quantum light reduces the noise level, thus obtaining better information about the image, in particular the sample contours.

“With quantum light, the noise level and therefore randomness are reduced, so that better information about the image is obtained, in particular about the sample edges, which, in the end, is essential to recognize concentrations, depths, heights of the samples, etc. ”, summarizes Cuevas.

According to the authors, the results obtained are very promising and reveal a completely new way of obtaining images with this technique.

“This innovative device has proven to have incredible capabilities that can definitely be exploited in a variety of applications, ranging from materials science, analysis of transparent surfaces to ensure the quality of flexible electronics, quantum cryptography for secure communications or even ultra-sensitive imaging of microorganisms. , like viruses and molecules”, says Valerio Pruneri, another of the ICFO co-authors.

Reference:

Camphausen et al. “A quantum enhanced wide-field phase imager.” Advances in Science, 2021.

ICFO researchers Robin Camphausen, Álvaro Cuevas, Luc Duempelmann, Roland Terborg and Ewelina Wajs participated in the study, led by ICREA professor Valerio Pruneri, in collaboration with Simone Tisa and André Ruggeri of Micro Devices Alessandro (MPD) and Iris Cusini of the University Milan Polytechnic (Italy) and Fabian Steinlechner from the Fraunhofer Institute for Applied Optics and Precision Engineering (Germany).

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