Quantum light allows imaging with sensitivity, speed and resolution beyond the reach of other techniques. Applications in biology are particularly important, because the best conventional microscopes are often severely constrained by photodamage to the specimen. Here, I will present experiment work from my lab applying squeezed light, a form of quantum light, to imaging of molecular vibrations. If time permits, I will also discuss work on quantum single-molecule imaging.
Quantum light allows imaging with sensitivity, speed and resolution beyond the reach of other techniques. Applications in biology are particularly important, because the best conventional microscopes are often severely constrained by photodamage to the specimen. Here, I will present experiment work from my lab applying squeezed light, a form of quantum light, to imaging of molecular vibrations. If time permits, I will also discuss work on quantum single-molecule imaging.
State-of-the-art microscopes use intense lasers that can severely disturb biological processes, function and viability. This introduces hard limits on performance that only quantum photon correlations can overcome. In this talk I will report recent work from my laboratory which demonstrates this absolute quantum advantage [1]. We show, specifically, that quantum correlations enable signal-to-noise beyond the photodamage-free capacity of conventional microscopy. Broadly, this represents the first demonstration that quantum correlations can allow sensing beyond the limits introduced by optical intrusion upon the measurement process. We achieve this in a coherent Raman microscope, which we use to image molecular bonds within a cell with both quantum-enhanced contrast and sub-wavelength resolution. This allows the observation of nanoscale biological structures that would otherwise not be resolved. Coherent Raman microscopes allow highly selective biomolecular finger-printing in unlabelled specimens, but photodamage is a major roadblock for many applications. By showing that this roadblock can be overcome, our work provides a path towards order-of-magnitude improvements in both sensitivity and imaging speed.
Much of our progress in understanding microscale biology has been powered by advances in microscopy. For instance, super-resolution microscopes allow the observation of biological structures at near-atomic-scale resolution, while multi-photon microscopes allow imaging deep into tissue. However, biological structures and dynamics still often remain out of reach of existing microscopes, with further advances in signal-to-noise, resolution and speed needed to access them. In many cases, the performance of microscopes is now limited by quantum effects – such as noise due to the quantisation of light into photons or, for multi-photon microscopes, the low cross-section of multi-photon scattering. These limitations can be overcome by exploiting features of quantum mechanics such as entanglement. Quantum effects can also provide new ways to enhance the performance of microscopes, such as new super-resolution techniques and new techniques to image at difficult to reach wavelengths. This review provides an overview of these various ways in which quantum techniques can improve microscopy, including recent experimental progress. It seeks to provide a realistic picture of what is possible, and what the constraints and opportunities are.
Quantum-enhanced metrology techniques offer ultra-precise timekeeping, allowing for breakthroughs in navigation systems, global positioning, medical and Biological imaging. Quantum metrology, a core application of quantum technologies, leverages non-classical states of light (such as entanglement and squeezing) to enhance measurement precision, sensitivity, and resolution beyond the classical limits, particularly the shot-noise limit. Its application to bio imaging and microscopy offers significant advantages for studying delicate biological specimens, which are often susceptible to damage from the intense light typically required by conventional high-resolution methods. The abstract highlights the potential of quantum properties of light to revolutionize bio imaging by providing a non-invasive, highly sensitive, and high-resolution platform for observing biological processes at fundamental scales.
Nonlinear optical processes are used in biological microscopy to surpass the diffraction limit on resolution, image deeper into brain tissues, and identify biomolecules without exogenous labels. These techniques typically require high optical intensities to increase the strength of the nonlinear interactions, which can perturb native biochemistry and damage or kill living samples. Stimulated Raman scattering (SRS) microscopy visualizes the spatial distribution of molecules using a nonlinear interaction between light and chemically specific molecular vibrations. However, the detection of biomolecules at low concentrations is limited by the total photon dose that can be applied before photodamage alters the sample, and photon shot noise sets the minimum achievable noise floor for most microscopes. Here we demonstrate a cavity-enhanced SRS microscope that is more sensitive than an equivalent conventional SRS microscope by up to 8.3(7) dB in spectroscopy and 8.6(1) dB in cell imaging. These results approach quantum limits on sensitivity and demonstrate that quantum states of light are sufficient but not necessary to enhance the sensitivity of microscopy techniques that are limited by photodamage.
Stimulated Raman scattering (SRS) microscopy is a powerful label-free imaging technique that probes the vibrational response of chemicals with high specificity and sensitivity. High-power, quantum-enhanced SRS microscopes have been recently demonstrated and applied to polymers and biological samples. Quantum correlations, in the form of squeezed light, enable the microscopes to operate below the shot noise limit, enhancing their performance without increasing the illumination intensity. This addresses the signal-to-noise ratio (SNR) and speed constraints introduced by photodamage in shot noise-limited microscopes. Previous microscopes have either used single-beam squeezing, but with insufficient brightness to reach the optimal ratio of pump-to-Stokes intensity for maximum SNR, or have used twin-beam squeezing and suffered a 3 dB noise penalty. Here we report a quantum-enhanced Raman microscope that uses a bright squeezed single-beam, enabling operation at the optimal efficiency of the SRS process. The increase in brightness leads to multimode effects that degrade the squeezing level, which we partially overcome using spatial filtering. We apply our quantum-enhanced SRS microscope to biological samples and demonstrate quantum-enhanced multispectral imaging of living cells. The imaging speed of 100×100 pixels in 18 seconds allows the dynamics of cell organelles to be resolved. The SNR achieved is compatible with video-rate imaging, with the quantum correlations yielding a 20% improvement in imaging speed compared to shot noise-limited operation.
Quantum imaging can be defined as an area of quantum optics that investigates the ultimate performance limits of optical imaging allowed by the quantum nature of light. Quantum Imaging techniques possess a high potential for improving the performance in recording, storage, and readout of optical images beyond the limits set by the standard quantum level of fluctuations known as the shot noise. This talk aims at giving an overview of the fundamentals of Quantum Imaging as well as its most important directions. We shall discuss generation of the spatially multimode squeezed states of light be means of a travelling-wave optical parametric amplifier. We shall demonstrate that this kind of light allows us to reduce the spatial fluctuations of the photocurrent in a properly chosen homodyne detection scheme with a highly efficient CCD camera. It will be shown that using the amplified quadrature of the light wave in a travelling-wave optical parametric amplifier, one can perform noiseless amplification of optical images. We shall provide recent experimental results demonstrating a single-shot noiseless image amplification by a pulsed optical parametric amplifier. One of important experimental achievements of Quantum Imaging, coined in the literature as quantum laser pointer, is a precise measurement of position and transverse displacement of a laser beam with resolution beyond the limit imposed by the shot noise. We shall describe briefly the idea of the experiment in which the transverse displacement of a laser beam was measured with resolution of the order of Angstrom. The problem of precise measurement of transverse displacement of a light beam brings us to a more general question about the quantum limits of optical resolution. The classical resolution criterion, derived in the nineteen century by Abbe and Rayleigh, states that the resolution of an optical instrument is limited by diffraction and is related to the wavelength of the light used in the imaging scheme. However, it was for a long time recognised in the literature that in some cases when one has some a priori information about the object, one can improve the resolution beyond the Rayleigh limit using the so-called super-resolution techniques. As a final topic in this talk, we shall discuss the quantum limits of optical super-resolution. In particular, we shall formulate the standard quantum limit of super-resolution and demonstrate how one can go beyond this limit using specially designed multimode squeezed light.