Single-photon atomic force microscopy.

In the last few years, an array of novel technologies, especially the big family of scanning probe microscopy, now often integrated with other powerful imaging tools such as laser confocal microscopy and total internal reflection fluorescence microscopy, have been widely applied in the investigation of biomolecular interactions and dynamics. But it is still a great challenge to directly monitor the dynamics of biomolecular interactions with high spatial and temporal resolution in living cells. An innovative method termed "single-photon atomic force microscopy" (SP-AFM), superior to existing techniques in tracing biomolecular interactions and dynamics in vivo, was proposed on the basis of the combination of atomic force microscopy with the technologies of carbon nanotubes and single-photon detection. As a unique tool, SP-AFM, capable of simultaneous topography imaging and molecular identification at the subnanometer level by synchronous acquisitions and analyses of the surface topography and fluorescent optical signals while scanning the sample, could play a very important role in exploring biomolecular interactions and dynamics in living cells or in a complicated biomolecular background.