More than 27 years ago at the IBM Almaden Research Center, low temperature high resolution spectroscopy experiments aimed at establishing the ultimate limits to optical storage in solids led to the first optical detection and spectroscopy of a single molecule in the condensed phase. At this unexplored ultimate limit, many surprises occurred where single molecules showed both spontaneous changes (blinking) and light-driven control of emission. In the 1990, optical detection of single molecules at room temperature blossomed in polymers and cells, serving as a local probe of a variety of complex environments without ensemble averaging. Surprises occurred here, too, including blinking and switching of single green fluorescent protein variants. In 2006, several groups showed that the optical diffraction limit of ~200 nm can be circumvented with single molecules to achieve super-resolution fluorescence microscopy. Essential to this is the combination of single-molecule fluorescence imaging with active control of the emitting concentration and sequential localization of single fluorophores decorating a structure. Super resolution microscopy has opened up a new frontier in which biological structures and behavior in complex environments can be observed with resolutions down to 20-40 nm and below. Today, even in the “conventional” single-molecule tracking regime where the motions of individual molecules are recorded rather than the shapes of extended structures, much can still be learned about complex nanoscale processes.

Story of single-molecule detection and spectroscopy and the surprises leading to super-resolution microscopy and beyond

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.