Quantum Enhanced Raman Spectroscopy for bioimaging applications

In the QuRAMAN project we will develop a novel quantum Raman microscope, which pushes forward the field of optical microscopy for bio-medical and bio-imaging use. We will exploit a new paradigm of quantum bio-optical measurements, which uses pulsed non-classical squeezed light combined with stimulated Raman scattering (SRS). SRS is a powerful tool for studying the spatio-temporal dynamics of molecular bonds in e.g. biological specimens with high sensitivity and speed.

Raman spectroscopy is an ideal contrasting method for chemically-resolved microscopy with no prior preparation or fluorescent tagging of the target molecule required. However, the major challenge for Raman sensing is the relative weakness of the Raman response, which is orders of magnitude weaker than fluorescence. The sensitivity and speed of state-of-the-art stimulated Raman scattering (SRS) spectroscopy are currently limited by the shot-noise of the light beam probing the Raman process.

In principle, the sensitivity can be arbitrarily improved by simply increasing the power of the input beams. However, in biological systems, and especially in living biological specimens, the optical intensity levels must be kept below certain thresholds to avoid damaging or changing the biological dynamics and thereby leading to erroneous results.

SRS employs two laser beams, known as the pump and probe (Stokes) beams, where at least one of the beams is tunable, to coherently excite a selected molecular vibration of the system under investigation. If the vibrational frequency of the chemical bond matches the frequency difference of the pump and probe lasers, the Raman interaction is stimulated and, as a result, significantly amplified by orders of magnitudes. In the stimulated Raman effect, a photon is annihilated from the pump beam and, simultaneously, a Raman-shifted photon is created in the background noise of the probe beam. To detect the stimulated scattering of photons from pump to probe, a modulation scheme is often employed. An intensity modulation is applied to one of the two beams and gets transferred to the other beam by SRS. The resulting modulation is detected with an intensity detector and a lock-in amplifier.

The precision by which the Raman signal can be measured depends on the background noise of the probe beam, which is fundamentally limited by the shot noise when the probe beam is in a coherent state produced by a conventional laser. By instead emplying amplitude squeezed states of light, the sensitivity can e improved without increasing the optical intensities.

During this project, the following main features will be developed and evaluated:

1. Development of the quantum Raman microscope.
2. Application to human tissue to support fast, objective, and reliable histopathological lung cancer screening.
3. OEM light source and compact microscope will be provided as plug&play modules, for supporting bioimaging and quantum technologies in education, science, and industry

Project Coordinator

Michael Lassen 

Danish Fundamental Metrology A/S