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.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.

Scientific ReportsJul 29, 20251 citation

Full-field cavity enhanced microscopy techniques

Stefan Nimmrichter, Chi-Fang Chen, Brannon B. Klopfer +2 more

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.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.

arXiv:1704.05217Journal of Physics PhotonicsDec 7, 20187 citations

Quantum-enhanced stimulated Brillouin scattering spectroscopy and imaging

Tian Li, Fu Li, Xinghua Liu +2 more

Brillouin microscopy is an emerging label-free imaging technique used to assess local viscoelastic properties. Quantum-enhanced stimulated Brillouin scattering is demonstrated using low power continuous-wave lasers at 795 nm. A signal-to-noise ratio enhancement of 3.4 dB is reported by using two-mode intensity-difference squeezed light generated with the four-wave mixing process in atomic rubidium vapor. The low optical power and the excitation wavelengths in the water transparency window have the potential to provide a powerful bio-imaging technique for probing mechanical properties of biological samples prone to phototoxicity and thermal effects. The performance enhancement affordable through the use of quantum light may pave the way for significantly improved sensitivity that cannot be achieved classically. The proposed method for utilizing squeezed light for enhanced stimulated Brillouin scattering can be easily adapted for both spectroscopic and imaging applications in biology.Brillouin microscopy is an emerging label-free imaging technique used to assess local viscoelastic properties. Quantum-enhanced stimulated Brillouin scattering is demonstrated using low power continuous-wave lasers at 795 nm. A signal-to-noise ratio enhancement of 3.4 dB is reported by using two-mode intensity-difference squeezed light generated with the four-wave mixing process in atomic rubidium vapor. The low optical power and the excitation wavelengths in the water transparency window have the potential to provide a powerful bio-imaging technique for probing mechanical properties of biological samples prone to phototoxicity and thermal effects. The performance enhancement affordable through the use of quantum light may pave the way for significantly improved sensitivity that cannot be achieved classically. The proposed method for utilizing squeezed light for enhanced stimulated Brillouin scattering can be easily adapted for both spectroscopic and imaging applications in biology.

arXiv:2112.02777OpticaJul 15, 202272 citations

Quantum-optimal nonlinear microscopy with classical light

Joshua L. Reynolds, S. C. Burd, Tzu-Chieh Yen +3 more

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.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.

arXiv:2512.04328Dec 3, 20250 citations

Quantum enhanced microscopy

Catxere A. Casacio

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.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.

Feb 17, 20211 citation

Broadly tunable quantum-enhanced Raman microscopy for advancing bioimaging

Dmitrii Akatev, Yijian Meng, Jonathan Brewer +3 more

Stimulated Raman scattering (SRS) microscopy has emerged as a powerful technique for probing the spatiotemporal dynamics of molecular bonds with exceptional sensitivity, resolution, and speed. However, classically, its performance remains fundamentally constrained by optical shot noise, which imposes a strict limit on detection sensitivity and speed. Here, we demonstrate a quantum-enhanced SRS microscopy platform that circumvents this barrier by harnessing amplitude-squeezed light. Specifically, we generate a Stokes beam with $5.2~\mathrm{dB}$ of amplitude squeezing using traveling-wave optical parametric amplification in second-order nonlinear waveguides, and combine it with a tunable coherent pump to access vibrational modes spanning from $1000$ to $3100~\mathrm{cm}^{-1}$ . Applied to quantum imaging of metabolites in biological tissue (pork muscle), our quantum-enhanced Raman microscope achieves an average noise suppression of $3.6~\mathrm{dB}$ and a $51\%$ enhancement in signal-to-noise ratio (SNR) -- to the best of our knowledge, the largest improvement reported to date in quantum-enhanced SRS microscopy of biological samples.Stimulated Raman scattering (SRS) microscopy has emerged as a powerful technique for probing the spatiotemporal dynamics of molecular bonds with exceptional sensitivity, resolution, and speed. However, classically, its performance remains fundamentally constrained by optical shot noise, which imposes a strict limit on detection sensitivity and speed. Here, we demonstrate a quantum-enhanced SRS microscopy platform that circumvents this barrier by harnessing amplitude-squeezed light. Specifically, we generate a Stokes beam with $5.2~\mathrm{dB}$ of amplitude squeezing using traveling-wave optical parametric amplification in second-order nonlinear waveguides, and combine it with a tunable coherent pump to access vibrational modes spanning from $1000$ to $3100~\mathrm{cm}^{-1}$. Applied to quantum imaging of metabolites in biological tissue (pork muscle), our quantum-enhanced Raman microscope achieves an average noise suppression of $3.6~\mathrm{dB}$ and a $51\%$ enhancement in signal-to-noise ratio (SNR) -- to the best of our knowledge, the largest improvement reported to date in quantum-enhanced SRS microscopy of biological samples.

physics.opticsCross-listedarXiv:2511.01430Optica QuantumNov 4, 20253 citations

5.2~\mathrm{dB}

of amplitude squeezing using traveling-wave optical parametric amplification in second-order nonlinear waveguides, and combine it with a tunable coherent pump to access vibrational modes spanning from

1000

3100~\mathrm{cm}^{-1}

. Applied to quantum imaging of metabolites in biological tissue (pork muscle), our quantum-enhanced Raman microscope achieves an average noise suppression of

3.6~\mathrm{dB}

and a

51\%

enhancement in signal-to-noise ratio (SNR) -- to the best of our knowledge, the largest improvement reported to date in quantum-enhanced SRS microscopy of biological samples.