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arXiv:1704.05217 · Journal of Physics Photonics

Full-field cavity enhanced microscopy techniques

Stefan Nimmrichter, Chi-Fang Chen, Brannon B. Klopfer, Mark A. Kasevich, Thomas Juffmann

Published Dec 7, 2018• 7 citations
arXivHTMLPDF

Abstract

The number of probe particles that is detected on a single pixel of a micrograph is finite, either due to source (low power), detector (low dynamic range) or specimen damage constraints. The sensitivity of an otherwise perfect microscope is then limited by the statistical fluctuations in the number of detected particles. It is thus crucial to strive for the optimal signal-to-noise ratio per detected photon. Here we analytically and numerically compare three different contrast enhancing techniques that are all based on self-imaging cavities: CW cavity enhanced microscopy, cavity ring-down microscopy and multi-pass microscopy. We show that all three schemes can lead to sensitivities beyond those achievable with a single pass.

DOI
10.1088/2515-7647/aae228

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The number of probe particles that is detected on a single pixel of a micrograph is finite, either due to source (low power), detector (low dynamic range) or specimen damage constraints. The sensitivity of an otherwise perfect microscope is then limited by the statistical fluctuations in the number of detected particles. It is thus crucial to strive for the optimal signal-to-noise ratio per detected photon. Here we analytically and numerically compare three different contrast enhancing techniques that are all based on self-imaging cavities: CW cavity enhanced microscopy, cavity ring-down microscopy and multi-pass microscopy. We show that all three schemes can lead to sensitivities beyond those achievable with a single pass.
Microscopy of biological specimens often requires low light levels to avoid damage. This yields images impaired by shot noise. An improved measurement accuracy at the Heisenberg limit can be achieved exploiting quantum correlations. If sample damage is the limiting resource, an equivalent limit can be reached by passing photons through a specimen multiple times sequentially. Here we use self-imaging cavities and employ a temporal post-selection scheme to present full-field multi-pass polarization and transmission micrographs with variance reductions of 4.4±0.8 dB (11.6±0.8 dB in a lossless setup) and 4.8±0.8 dB, respectively, compared with the single-pass shot-noise limit. If the accuracy is limited by the number of detected probe particles, our measurements show a variance reduction of 25.9±0.9 dB. The contrast enhancement capabilities in imaging and in diffraction studies are demonstrated with nanostructured samples and with embryonic kidney 293T cells. This approach to Heisenberg-limited microscopy does not rely on quantum state engineering.
Microscopy gives access to spatially resolved dynamics in different systems, from biological cells to cold atoms. A big challenge is maximizing the information per used probe particle to limit the damage to the probed system. We present a cavity-enhanced continuous-wave microscopy approach that provides enhanced signal-to-noise ratios at fixed damage. Employing a self-imaging 4f cavity, we show contrast enhancement for controlled test samples as well as biological samples. For thick samples, the imaging cavity leads to a new form of dark-field microscopy, where the separation of scattered and unscattered light is based on optical path length. We theoretically show that enhanced signal, signal-to-noise, and signal-to-noise per damage are also retrieved when the cavity cannot be stabilized. Our results provide an approach to cavity-enhanced microscopy with unstabilized cavities and might be used to enhance the performance of dispersive imaging of ultracold atoms.
Microscopy gives access to spatially resolved dynamics in different systems, from biological cells to cold atoms. A big challenge is maximizing the information per used probe particle to limit the damage to the probed system. We present a cavity-enhanced continuous-wave microscopy approach that provides enhanced signal-to-noise ratios at fixed damage compared to standard single-pass microscopy. Employing a self-imaging 4f cavity, we show contrast enhancement for controlled test samples as well as biological samples. For thick samples, the imaging cavity leads to a new form of dark-field microscopy, where the separation of scattered and unscattered light is based on optical path length. We theoretically show that enhanced signal, signal-to-noise, and signal-to-noise per damage are also retrieved when the cavity is not length-stabilized. Our results provide an approach to cavity-enhanced microscopy with non-length-stabilized cavities and might be used to enhance the performance of dispersive imaging of ultracold atoms.
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.
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.
We present progress towards demonstrating multi-passed stimulated Raman scattering microscopy and multi-passed transmission electron microscopy. A multi-pass microscope interrogates a sample multiple times in a cyclical and deterministic fashion. This can lead to a metrological advantage for imaging weak scatterers. The enhanced sensitivity can yield a significant reduction in damage imparted to biological samples or can reduce image acquisition time. The approach compares favorably with imaging techniques using squeezed or entangled probe states, but avoids the technical complexity associated with the production of such states.