Physical principles over governing the generation and propagation of Raman signals in biological tissues: A review

Raman spectroscopy represents a distinctively strong, labelless mechanism of investigating the biochemical structure of biological tissues, however its diagnostic capability is inherently restricted by the physics of the molecular scattering and the photon transport in discoloured stationary matter. This review gives a combined analysis of the physical concepts of signal generation, propagation, attenuation, and detection of Raman in living conditions. We start with the quantum mechanical explanation of the way Raman scattering occurs and the very small cross-sections which restrict inherent signal yield. Significant sources of noise, including fluorescence, thermal background and shot noise, are considered relative to their effect on the signal-to-noise ratios possible. Electromagnetic and chemical SERS as enhancement mechanisms are not only discussed but also emphasized strictly physically in order to bring out the potential of such techniques and their limitations. On these premises, we establish the theoretical confines of Raman tissue diagnostics as well as state the prevailing physical limitations that limit clinical implementation. And lastly we outline new future directions, such as wavefront shaping, time-gated detection, engineered nanoparticles, and multimodal photonic integration which could help Raman technologies to approach their ultimate physical limits.