Multiphoton effects have been predicted by the PhD student Maria Goeppert in the twenties of the last century. However, it took more than 30 years to prove her theory. In 1961, one year after the discovery of the laser, Kaiser et al. demonstrated two-photon excited fluorescence. Shortly after the introduction of a first ultrashort laser microscope, Denk et al. published in 1990 on a two-photon microscope for cell imaging. Piston et al. and König et al. investigated the cellular autofluorescence and Masters et al. the tissue autofluorescence with a two-photon microscope. In 2003, the first peer-reviewed publication on a clinical two-photon imaging system, a so-called multiphoton tomograph “DermaInspect”, appeared.
Later on, the CE certified tomograph MPTflex with an optomechanical arm and 360° measurement head was introduced by the company JenLab. Later the clinical two-photon GRIN lens microendoscope was launched. The introduction of a second NIR ultrashort laser beam provided the possibility to perform additional Raman imaging.
K. König, and I. Riemann, "High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution ," J Biomed Opt 8 (2003) 432-439
K. König, H. G. Breunig, R. Bückle, M. Kellner-Höfer, M. Weinigel, E. Büttner, W. Sterry, J. Lademann, "Optical Skin Biopsies by clinical CARS and Multiphoton Fluorescence/SHG Tomography“ Laser Physics Letters 8 (2011) 1-4
1927: Prediction of multiphoton effects
1961: First SHG experiment
1961: First two-photon fluorescence experiment
1989: Two-photon microscope
1998: Two-photon microscopy on volunteers arm
2002: First in vivo MPT on man
2002: First two-photon FLIM on man
2011: First in vivo CARS on man
Photo Maria Goeppert-Mayer by ENERGY.GOV (HD.3A.050) [Public domain], via Wikimedia Commons