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Broadly Tunable Quantum Enhanced Raman Microscopy for Advancing Bioimaging

Dmitrii Akatev, Yijian Meng, Jonathan Brewer, Maria Chekhova, Ulrik L. Andersen, Mikael Lassen

TL;DR

This work addresses the shot-noise limit in stimulated Raman scattering microscopy by introducing a quantum-enhanced platform that uses amplitude-squeezed Stokes light. By generating a bright amplitude-squeezed Stokes beam with a pulsed OPA in a PPLN waveguide and combining it with a tunable Raman pump, the authors achieve broadband access from $1000-3100 cm^{-1}$ and demonstrate a $3.6$ dB noise reduction with a 51% SNR improvement in pork muscle tissue. The study extends QE-SRS to both fingerprint and CH-stretch spectral regions and reports robust, band-dependent enhancements across multiple vibrational markers, including proteins and lipids. These results point to higher sensitivity, faster acquisition, and reduced photodamage for label-free bioimaging, with potential for real-time clinical applications and deeper molecular discrimination.

Abstract

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.

Broadly Tunable Quantum Enhanced Raman Microscopy for Advancing Bioimaging

TL;DR

This work addresses the shot-noise limit in stimulated Raman scattering microscopy by introducing a quantum-enhanced platform that uses amplitude-squeezed Stokes light. By generating a bright amplitude-squeezed Stokes beam with a pulsed OPA in a PPLN waveguide and combining it with a tunable Raman pump, the authors achieve broadband access from and demonstrate a dB noise reduction with a 51% SNR improvement in pork muscle tissue. The study extends QE-SRS to both fingerprint and CH-stretch spectral regions and reports robust, band-dependent enhancements across multiple vibrational markers, including proteins and lipids. These results point to higher sensitivity, faster acquisition, and reduced photodamage for label-free bioimaging, with potential for real-time clinical applications and deeper molecular discrimination.

Abstract

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

Paper Structure

This paper contains 9 sections, 1 equation, 4 figures.

Table of Contents

  1. Introduction
  2. Stimulated Raman microscopy setup
  3. Full scheme
  4. Preparation of amplitude-squeezed light
  5. Tunability of QE-SRS microscope
  6. Quantum-enhanced SRS bioimaging
  7. QE-SRS on a pork muscle tissue
  8. Multifrequency biological imaging
  9. Conclusion

Figures (4)

  • Figure 1: Block diagram of the main parts of the quantum-enhanced SRS microscopy setup. PicoEmerald: pulsed laser (11 ps@80Mhz rep. rate). DM: dichroic mirrors. OPA: Squeezer, source of amplitude-squeezed light. SHG: second harmonic generation source for pumping OPA. PBS: polarizing beam splitter. HWP: Half-wave plates. EOM: electro-optic modulator for generating a 19.3 MHz modulation on the Raman pump. MO 50$\times$: microscope objective 50$\times$. BP 1064: 1064 nm bandpass filter. HBS: harmonic beam splitter. LPF: long-pass optical filter. SPF: short-pass optical filter. XYZ stage: 3D raster-scanning stage. Detector: InGaAs PD, home-made resonant photodetector. Moku: field-programmable gate array for system control and data acquisition.
  • Figure 2: (a) White-light wide-field image of a polystyrene microparticle; SRS images of the same particle at Raman shifts (b) 1003 cm$^{-1}$ (symmetric ring-breathing mode); (c) 1600 cm$^{-1}$ (skeletal C=C stretching mode); (d) 3050 cm$^{-1}$ (aromatic C–H stretching mode).
  • Figure 3: (a) White-light wide-field image of the pork muscle tissue sample. (b) SRS image acquired at 2940 cm$^{-1}$ in the same region as the wide-field image. (c) Signal-to-noise ratio of the SRS signal from the region indicated by the white square in panel (b), plotted as a function of Raman pump power for squeezed (blue) and coherent (red) Stokes beams of equal power. Maps of SRS signal-to-noise ratio for (d) coherent and (e) squeezed Stokes beams.
  • Figure 4: Quantum-enhanced SRS images of pork muscle tissue acquired at: (a) 1450 cm$^{-1}$, (b) 1650 cm$^{-1}$, (c) 2850 cm$^{-1}$, and (d) 2940 cm$^{-1}$. Left panels show the SRS intensity obtained using a coherent Stokes beam; middle and right panels display the corresponding SNR measurements for coherent and amplitude-squeezed Stokes beams, respectively. (e) White-light wide-field image of the sample. (f) and (g) Cross-sectional profiles of the SNR along Y = 0 $\mu m$ and Y = 15 $\mu m$ from panel (d), respectively, comparing the coherent (red) and amplitude-squeezed (blue) Stokes beam configurations.