Toward Quantum Enhancement in Biological Molecular Imaging

Christian Schnell

Warwick P. Bowen, Catxere A. Casacio, Lars S. Madsen +5 more

State-of-the-art microscopes use intense lasers that can severely disturb biological processes, function and viability. This introduces hard limits on performance that only quantum photon correlations can overcome. Here we demonstrate this absolute quantum advantage, achieving signal-to-noise beyond the photodamage-free capacity of conventional microscopy. We achieve this in a coherent Raman microscope, which we use to image molecular bonds within a cell with both quantum-enhanced contrast and sub-wavelength resolution. This allows the observation of nanoscale biological structures that would otherwise not be resolved. Coherent Raman microscopes allow highly selective biomolecular finger-printing in unlabelled specimens, but photodamage is a major roadblock for many applications. By showing that this roadblock can be overcome, our work provides a path towards order-of-magnitude improvements in both sensitivity and imaging speed.

Pengcheng Fu, Xiao Liu, Siming Wang +10 more

Label-free optical microscopy through absorption or scattering spectroscopy provides fundamental insights across biology and materials science, yet its sensitivity remains fundamentally limited by photon shot noise. While recent demonstrations of quantum nonlinear microscopy show sub-shot-limited sensitivity, they are intrinsically limited by availability of high peak-power squeezed light sources. Here, we introduce squeezing-enhanced photothermal (SEPT) microscopy, a quantum imaging technique that leverages twin-beam quantum correlations to detect absorption induced signals with unprecedented sensitivity. SEPT achieves 3.5 dB noise suppression beyond the standard quantum limit, enabling a 2.5-fold increase in imaging throughput or 31% reduction in pump power, while providing an unmatched versatility through the intrinsic compatibility between continuous-wave squeezing and photothermal modulation. We showcase SEPT applications by providing high-precision characterization of nanoparticles and revealing subcellular structures, such as cytochrome c, that remain undetectable under shot-noise-limited imaging. By combining label-free contrast, quantum-enhanced sensitivity, and compatibility with existing microscopy platforms, SEPT establishes a new paradigm for molecular absorption imaging with far-reaching implications in cellular biology, nanoscience, and materials characterization.

Michael A. Taylor

Hugo Defienne, Warwick P. Bowen, Maria V. Chekhova +5 more

Zicong Xu, Sho Nitanai, Kenichi Oguchi +1 more

Quantum-enhanced stimulated Raman scattering (QE-SRS) microscopy sits at the intersection of biomedical imaging, laser microscopy, and quantum optics toward realizing sensitive molecular-vibrational imaging. This Perspective explores the current status of this emerging field, integrating viewpoints from these diverse disciplines to highlight its potential for advancing biological and medical imaging. We discuss key challenges and future directions in leveraging quantum light to push the sensitivity limits of SRS microscopy, paving the way for next-generation imaging modalities.