Pharmaceutical applications of non-linear imaging.

Non-linear optics encompasses a range of optical phenomena, including two- and three-photon fluorescence, second harmonic generation (SHG), sum frequency generation (SFG), difference frequency generation (DFG), third harmonic generation (THG), coherent anti-Stokes Raman scattering (CARS), and stimulated Raman scattering (SRS). The combined advantages of using these phenomena for imaging complex pharmaceutical systems include chemical and structural specificities, high optical spatial and temporal resolutions, no requirement for labels, and the ability to image in an aqueous environment. These features make such imaging well suited for a wide range of pharmaceutical and biopharmaceutical investigations, including material and dosage form characterisation, dosage form digestion and drug release, and drug and nanoparticle distribution in tissues and within live cells. In this review, non-linear optical phenomena used in imaging will be introduced, together with their advantages and disadvantages in the pharmaceutical context. Research on pharmaceutical and biopharmaceutical applications is discussed, and potential future applications of the technology are considered.