Nonlinear magic: multiphoton microscopy in the biosciences

Nat Biotechnol. 2003 Nov;21(11):1369-77. doi: 10.1038/nbt899.


Multiphoton microscopy (MPM) has found a niche in the world of biological imaging as the best noninvasive means of fluorescence microscopy in tissue explants and living animals. Coupled with transgenic mouse models of disease and 'smart' genetically encoded fluorescent indicators, its use is now increasing exponentially. Properly applied, it is capable of measuring calcium transients 500 microm deep in a mouse brain, or quantifying blood flow by imaging shadows of blood cells as they race through capillaries. With the multitude of possibilities afforded by variations of nonlinear optics and localized photochemistry, it is possible to image collagen fibrils directly within tissue through nonlinear scattering, or release caged compounds in sub-femtoliter volumes.

Publication types

  • Review

MeSH terms

  • Biological Science Disciplines / instrumentation
  • Biological Science Disciplines / methods
  • Biological Science Disciplines / trends
  • Equipment Design
  • Image Enhancement / instrumentation*
  • Image Enhancement / methods*
  • Imaging, Three-Dimensional / instrumentation*
  • Imaging, Three-Dimensional / methods*
  • Imaging, Three-Dimensional / trends
  • Microscopy, Confocal / instrumentation
  • Microscopy, Confocal / methods
  • Microscopy, Confocal / trends
  • Microscopy, Fluorescence, Multiphoton / instrumentation*
  • Microscopy, Fluorescence, Multiphoton / methods*
  • Microscopy, Fluorescence, Multiphoton / trends
  • Nonlinear Dynamics
  • Transducers*