Recovering both amplitude and phase information from a system is a fundamental goal of optical imaging. At the same time, it is crucial to operate at low photon doses to avoid altering the sample, particularly in biological applications. Quantum imaging provides a powerful route to extract more information per photon than classical techniques, which are ultimately limited by shot-noise. However, the trade-off between quantum noise reduction and spatial resolution has long been regarded as a major obstacle to the application of quantum techniques to small cellular and sub-cellular structures, where they could offer the greatest benefits. Here, we overcome this limitation by demonstrating sub-shot-noise quantitative phase imaging of biological cells based on the transport-of-intensity equation, enabling high-fidelity, label-free imaging of key cellular and sub-cellular features. We achieve high-resolution phase imaging limited only by the numerical aperture, while simultaneously obtaining a resolution-independent quantum advantage. Unlike other quantum imaging approaches, our method operates in a quasi-single-shot, wide-field configuration, retrieves both phase and amplitude information, and does not rely on interferometric measurements, making it intrinsically fast and stable. These results pave the way for the immediate application of sub-shot-noise imaging in biological microscopy.
Recovering both amplitude and phase information from a system is a fundamental goal of optical imaging. At the same time, it is crucial to operate at low photon doses to avoid altering the sample, particularly in biological applications. Quantum imaging provides a powerful route to extract more information per photon than classical techniques, which are ultimately limited by shot-noise. However, the trade-off between quantum noise reduction and spatial resolution has long been regarded as a major obstacle to the application of quantum techniques to small cellular and sub-cellular structures, where they could offer the greatest benefits. Here, we overcome this limitation by demonstrating sub-shot-noise quantitative phase imaging of biological cells based on the transport-of-intensity equation, enabling high-fidelity, label-free imaging of key cellular and sub-cellular features. We achieve high-resolution phase imaging limited only by the numerical aperture, while simultaneously obtaining a resolution-independent quantum advantage. Unlike other quantum imaging approaches, our method operates in a quasi-single-shot, wide-field configuration, retrieves both phase and amplitude information, and does not rely on interferometric measurements, making it intrinsically fast and stable. These results pave the way for the immediate application of sub-shot-noise imaging in biological microscopy.
Recovering both amplitude and phase information from a system is a fundamental goal of optical imaging. At the same time, it is crucial to operate at low photon doses to avoid altering the sample, particularly in biological applications. Quantum imaging provides a powerful route to extract more information per photon than classical techniques, which are ultimately limited by shot-noise. However, the trade-off between quantum noise reduction and spatial resolution has long been regarded as a major obstacle to the application of quantum techniques to small cellular and sub-cellular structures, where they could offer the greatest benefits. Here, we overcome this limitation by demonstrating sub-shot-noise quantitative phase imaging of biological cells based on the transport-of-intensity equation, enabling high-fidelity, label-free imaging of key cellular and sub-cellular features. We achieve high-resolution phase imaging limited only by the numerical aperture, while simultaneously obtaining a resolution-independent quantum advantage. Unlike other quantum imaging approaches, our method operates in a quasi-single-shot, wide-field configuration, retrieves both phase and amplitude information, and does not rely on interferometric measurements, making it intrinsically fast and stable. These results pave the way for the immediate application of sub-shot-noise imaging in biological microscopy.
Recently, several proof of principle experiments have demonstrated the advantages of quantum technologies over classical schemes. The present challenge is to surpass the limits of proof of principle demonstrations to approach real applications. This letter presents such an achievement in the field of quantum enhanced imaging. In particular, we describe the realization of a sub-shot-noise wide field microscope based on spatially multi-mode non-classical photon number correlations in twin beams. The microscope produces realtime images of 8000 pixels at full resolution, for a 500 μm2 field of view, with noise reduced to 80% of the shot noise level (for each pixel), which is suitable for absorption imaging of complex structures. By fast post-elaboration, specifically applying a quantum enhanced median filter, the noise can be further reduced (to <30% of the shot noise level) by setting a trade-off with the resolution, thus achieving the best sensitivity per incident photon reported in absorption microscopy. A new microscope instantly captures thousands of photons from faint objects with signal-to-noise ratios exceeding classical limits. Imaging of sensitive objects, such as live cells, limits the optical power that lasers can apply. Now, Alice Meda from Italy's INRIM and colleagues have developed a microscope that ’squeezes‘ light to overcome intensity-limiting shot noise caused by quantum fluctuations of photons. Their sub-shot-noise microscope uses a nonlinear crystal to generate two high correlated light beams impossible for classical waves. Microscale pixels recorded intensities when one beam strikes a sample can have their shot noise reduced by 20% by subtracting correlated patterns from the second reference beam. This quantum-enhanced noise reduction enables the microscope to operate for high sensitive, dynamic, wide field, Q imaging applications.
Quantum entanglement and squeezing have significantly improved phase estimation and imaging in interferometric settings beyond the classical limits. However, for a wide class of non-interferometric phase imaging/retrieval methods vastly used in the classical domain, e.g., ptychography and diffractive imaging, a demonstration of quantum advantage is still missing. Here, we fill this gap by exploiting entanglement to enhance imaging of a pure phase object in a non-interferometric setting, only measuring the phase effect on the free-propagating field. This method, based on the so-called "transport of intensity equation", is quantitative since it provides the absolute value of the phase without prior knowledge of the object and operates in wide-field mode, so it does not need time-consuming raster scanning. Moreover, it does not require spatial and temporal coherence of the incident light. Besides a general improvement of the image quality at a fixed number of photons irradiated through the object, resulting in better discrimination of small details, we demonstrate a clear reduction of the uncertainty in the quantitative phase estimation. Although we provide an experimental demonstration of a specific scheme in the visible spectrum, this research also paves the way for applications at different wavelengths, e.g., X-ray imaging, where reducing the photon dose is of utmost importance.
In optical microscopy, as in any biological measurement performed with light, there is a compromise between increasing power to improve resolution and decreasing power to prevent photodamage to the biological structure. Quantum optics allows this compromise to be overcome, enabling improved precision without increased illumination intensity. This thesis demonstrates, for the first time, absolute quantum advantage in microscopy, with a specific focus on Stimulated Raman Scattering (SRS) microscopy.SRS microscopy is a powerful tool widely used in many fields, especially in biomedical sciences. It uses a two-photon process where the light is downshifted in frequency by being absorbed and subsequently inelastically scattered by the intrinsic molecular vibrations in the sample. Each element or molecule has a different response, allowing selective imaging of biological systems. SRS microscopy is particularly useful because it is label-free (no addition of dyes, beads or any implanted tracer), meaning that imaging contrast is achieved without modification of, or interference with, the specimen. Here I present our newly built state-of-the-art shot-noise limited SRS microscope. I also characterize the Raman microscope, describe the developped imaging system and show SRS spectroscopy and imaging of both polystyrene beads and living yeast cells.The quantisation of light introduces a fundamental uncertainty, or quantum noise, in both the amplitude and phase quadratures of an optical field. A squeezed state of light is a state of the optical field where the uncertainty of one of these quadratures is reduced below the quantum noise. Therefore, it provides an approach to reduce the noise level below this quantum noise limit and consequently increases measured signal-to-noise ratio. Here I describe the concepts involved in this technique and present our newly built light squeezer. I characterize the squeezing and show up to -1.3 dB of noise floor reduction for a 6 picosecond pulsed laser, which is the pulse duration that maximises the Raman interaction.In this thesis we apply squeezed states of light in SRS, developping a quantum-enhanced micro- scope. Our SRS Raman intensity noise is ∆I/I ≈ 10^(−7) and the measured quantum efficiency of the built photodiode is η = 72%. In this proof of principle we show a reduction of the noise floor of at least 13% below the quantum noise limit for Raman imaging of polystyrene beads and living yeast cells. This enhancement allowed us to resolve the cell membrane where with conventional microscope would be unresolvable. It also allowed sub-micron spatial resolution. The improved image contrast and reduced imaging time, while avoiding photodamage in the sample, surpasses the current state-of-the-art Raman microscopes and opens opportunities for new discoveries in biophysics.
Summary form only given. In the last years several proof of principle experiments have demonstrated the advantages of quantum technologies respect to classical schemes in imaging, metrology and sensing. The present challenge is to overcome the limits of proof of principle demonstrations to approach real applications. Here, we present the such an achievement in the field of quantum enhanced imaging. In particular, we describe the realization of a sub-shot-noise (SSN) wide field microscope (see Ref. [1]), based on spatially multi-mode non-classical photon number correlations [2]. The microscope produces real-time images of 8000 pixels at full resolution, for (500μm)2field-of-view, with noise reduced at 80% of the shot noise level in each pixel. This is suitable for absorption imaging of complex structures, like biological samples. By simple post-elaboration, specifically applying a “quantum enhanced median filter”, the noise is further reduced (less than 30% of the shot noise level) by setting a trade-off with the resolution. It realizes the best sensitivity per incident photon ever achieved in absorption microscopy.
Quantum correlation, such as entanglement and squeezing have shown to improve phase estimation in interferometric setups on one side, and non-interferometric imaging scheme of amplitude object on the other. In the last case, quantum correlation among a pair of beams leads to a sub-shot-noise readout of the image intensity pattern, where weak details, otherwise hidden in the noise, can be appreciated. In this paper we propose a technique which exploits entanglement to enhance quantitative phase retrieval of an object in a non-interferometric setting, i.e only measuring the propagated intensity pattern after interaction with the object. The method exploits existing technology, it operates in wide field mode, so does not require time consuming raster scanning and can operate with small spatial coherence of the incident field. This protocol can find application in optical microscopy and X-ray imaging, reducing the photon dose necessary to achieve a fixed signal-to-noise ratio.