Quantum-optimal nonlinear microscopy with classical light

TL;DR

This paper introduces a cavity-enhanced stimulated Raman scattering microscope that significantly improves sensitivity, approaching quantum limits, enabling better biological imaging with lower photodamage using classical light.

Contribution

The authors demonstrate a cavity-enhanced SRS microscopy technique that surpasses conventional methods in sensitivity, approaching quantum limits, without requiring quantum light sources.

Findings

Up to 8.3 dB sensitivity improvement in spectroscopy

Up to 8.6 dB enhancement in cell imaging

Approaches quantum limits on sensitivity

Abstract

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.