Quantum effects may help devise new imaging schemes that can overcome classical constraints posed by noise and diffraction. By using squeezed states of light in photonic force microscopy (PFM), scientists have demonstrated a 14% quantum enhancement of PFM's spatial resolution, imaging details of living yeast cells with a resolution of 10 nm.
Quantum effects may help devise new imaging schemes that can overcome classical constraints posed by noise and diffraction. By using squeezed states of light in photonic force microscopy (PFM), scientists have demonstrated a 14% quantum enhancement of PFM's spatial resolution, imaging details of living yeast cells with a resolution of 10 nm.
This thesis reports the development of a quantum enhanced microparticle tracking technique, which applied to measurements within living cells, allowed the first demonstrations of both biological measurements beyond the quantum noise limit and quantum enhanced spatial resolution within biology. The sensitivity of any optical measurement is limited by noise which follows from quantization of the electromagnetic field. This thesis theoretically characterizes the resulting quantum limit on particle tracking precision; both in the limit of perfect measurements and for the measurements used in real experiments, and theoretically establishes an experimental strategy which could allow the quantum limit to be surpassed via the application of non-classical light. Further, a computational tool is developed which allows rapid characterization of particle tracking experiments, thus providing researchers the benefit of rigorous theoretical predictions without requiring detailed calculations. Following this, classical technologies are developed which can improve microparticle tracking sensitivity and which are enabling steps toward integration of non-classical light. An interferometric strategy is described whereby signal-to-noise is improved by removing unwanted light from the detector. An optical lock-in technique is developed which eliminates low-frequency noise, thus allowing quantum noise limited performance at low frequencies. This is a crucial requirement for quantum enhanced measurements, and can also improve precision in classical experiments. Dark-field illumination is also explored as a method to remove unwanted background light, and the optimal illumination angle is calculated for our intended experiments. These advances are then applied in the development of the first quantum enhanced particle tracking apparatus. Squeezed states of light are used to improve particle tracking precision by 2.7 dB, demonstrating quantum enhanced microscopy for the first time. This was applied to perform the first measurements of living systems with quantum enhanced precision. Naturally occurring lipid particles were tracked within the cytoplasm of Saccharomyces cerevisiae yeast cells, with squeezed light enhancing precision by 2.4 dB. The thermal motion of these particles could then be analyzed to infer the viscosity and elasticity of the local environment, with squeezed light allowing 64% faster observations, thus improving the sensitivity to dynamic biological changes. This experiment was then extended to spatially resolved quantum imaging, with lipid particles used as scanning probes in a technique called photonic force microscopy. The particles sample variations in the local environment with resolution limited by measurement precision rather than the diffraction limit. The use of squeezed light was found to enhance spatial resolution by 14% at an absolute resolution level of 10 nm, comparable to leading classical experiments. This was the first demonstration of both sub-diffraction limited resolution and quantum enhanced resolution in biology, and places practical applications of quantum imaging within reach. Finally, the future challenges and prospects of quantum enhanced particle tracking are outlined.n
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.
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.
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.
The spatial resolution of an imaging apparatus is limited by the Rayleigh diffraction bound, a consequence of the imager's finite spatial extent. We show some N-photon strategies that permit resolution of details that are smaller than this bound, attaining either a 1∕N enhancement (standard quantum limit) or a 1∕N enhancement (Heisenberg-like scaling) over standard techniques. In the incoherent imaging regime, the methods presented are loss resistant, since classical light sources suffice. Our results may be of importance in many applications: microscopy, telescopy, lithography, metrology, etc.