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Structuring Quantum Light for Microscopy

Periodic Reporting for period 1 - SQiMic (Structuring Quantum Light for Microscopy)

Reporting period: 2022-10-01 to 2025-03-31

Optical microscopy is a crucial tool for biomedical research and medical diagnostics, offering structural and functional insights into biological specimens in a non-invasive and non-ionizing manner. However, it faces significant challenges when imaging small, weakly scattering objects (e.g. single cells) embedded in complex biological tissues, which induce optical aberrations and scattering. This issue becomes even more critical for samples that cannot be labelled or do not naturally emit light.
With the SQIMIC project, I take a major conceptual leap beyond the current paradigm by combining quantum imaging and light structuring to develop an innovative quantum "toolbox" for microscopy. This novel approach builds on my groundbreaking work demonstrating that wavefront shaping techniques - originally developed for laser light manipulation - can also be applied to higher orders of optical coherence. This enables precise control over quantum properties of light, such as entanglement.
Using this strategy, I explore genuine quantum imaging concepts, including quantum holography, quantum interference, and quantum illumination, to overcome the limitations of label-free classical microscopy. My goal is to image complex biological samples with unprecedented resolution, improved contrast, minimized aberrations, and reduced noise. Ultimately, I aim to create a quantum-enhanced microscope with exceptional performance, capable of imaging biological specimens without labeling or relying on their inherent light-emitting properties.
To achieve this, I have divided the work into three interconnected work packages (WPs):
• WP1: Quantum light structuring toolbox: Building on the ability to manipulate second-order coherence through wavefront shaping, I develop 5 quantum imaging methods based on entangled photon pairs (i.e. 5 distinct objectives). These methods aim to enhance classical imaging performance (resolution, noise resistance, and speed) and create new modalities.
• WP2: Development of quantum camera technology: Quantum imaging relies on the ability to capture quantum properties of light. I develop a fast imaging method to measure photon coincidences across multiple spatial locations, leveraging state-of-the-art single-photon sensitive cameras, FPGA circuits, and computational techniques.
• WP3: Construction of a quantum-enhanced microscope: This work package, starting in the middle of the third year, will integrate the advancements from WP1 and WP2 to build a practical quantum-enhanced microscope.
In terms of the work plan, I had initially planned to achieve three key objectives (two in WP1 and one in WP2) before the third year, which I successfully did. In two instances, I exceeded these objectives, opening up new research directions that were not part of the original Description of Action. Additionally, I delivered all promised deliverables, including publications, conference presentations, outreach activities, meetings, and datasets.
To date, I recognize three major achievements in our work:
1. Development of a novel adaptive optics approach using entangled photon pairs.
This work was published in Science [Science, 383(6687), 1142–1148 (2024)].
2. Development of a method to encode images in the quantum correlations of photons.
The results were published in Physical Review Letters [Phys. Rev. Lett., 133, 093601 (2024)].
3. Publication of a review article on quantum imaging in Nature Photonics.
[Nature Photonics, 18, 1024–1036 (2024)]. I was invited by the editor to coordinate this review, which highlights the contributions of my group to the field of quantum imaging and their recognition by the scientific community.
Among the different results already obtained, the development of a novel adaptive optics approach using entangled photon pairs, with the results reported in Science, 383(6687), 1142–1148 (2024), represents a significant advancement beyond the state of the art and is poised to have a substantial impact. This idea—unexpected and not fully planned at the start of the project—is extremely promising, as it could lead to a true paradigm shift in adaptive optics for microscopy. Its potential is so compelling that we are considering placing it at the core of WP3, which will begin in the third year of the project and focuses on the practical realization of a quantum microscope.
Furthermore, this work has strong potential for commercial application: it could be integrated as a new module into existing microscopes, which we are already exploring with collaborators specializing in microscopy for biology. The concept of this technique is described in the illustration attached to the project summary.
Concept of the new adaptive optics technique based on entangled photon pairs
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