Nobel Lecture: Single-molecule spectroscopy, imaging, and photocontrol: Foundations for super-resolution microscopy*

W. E. (William E.) Moerner
Rev. Mod. Phys. 87, 1183 – Published 21 October 2015

Abstract

The initial steps toward optical detection and spectroscopy of single molecules in condensed matter arose out of the study of inhomogeneously broadened optical absorption profiles of molecular impurities in solids at low temperatures. Spectral signatures relating to the fluctuations of the number of molecules in resonance led to the attainment of the single-molecule limit in 1989 using frequency-modulation laser spectroscopy. In the early 1990s, many fascinating physical effects were observed for individual molecules, and the imaging of single molecules as well as observations of spectral diffusion, optical switching and the ability to select different single molecules in the same focal volume simply by tuning the pumping laser frequency provided important forerunners of the later super-resolution microscopy with single molecules. In the room-temperature regime, imaging of single copies of the green fluorescent protein also uncovered surprises, especially the blinking and photoinduced recovery of emitters, which stimulated further development of photoswitchable fluorescent protein labels. Because each single fluorophore acts as a light source roughly 1 nm in size, microscopic observation and localization of individual fluorophores is a key ingredient to imaging beyond the optical diffraction limit. Combining this with active control of the number of emitting molecules in the pumped volume led to the super-resolution imaging of Eric Betzig and others, a new frontier for optical microscopy beyond the diffraction limit. The background leading up to these observations is described and selected current developments are summarized.

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  • Received 26 February 2015

DOI:https://doi.org/10.1103/RevModPhys.87.1183

© 2015 Nobel Foundation, Published by The American Physical Society

  • *The 2014 Nobel Prize for Chemistry was shared by Eric Betzig, Stefan W. Hell, and William E. Moerner. These papers are the text of the address given in conjunction with the award.

Authors & Affiliations

W. E. (William E.) Moerner

  • Departments of Chemistry and (by courtesy) of Applied Physics, Stanford University, Stanford, California 94305, USA

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Vol. 87, Iss. 4 — October - December 2015

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