Cited by 103Advanced Fluorescence Microscopy TechniquesSpectroscopy and Quantum Chemical StudiesPhotochemistry and Electron Transfer Studies

Single-molecule spectroscopy and imaging over the decades

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Moerner, W. E., Shechtman, Yoav, Wang, Quan·2015·Faraday Discussions

Abstract

As of 2015, it has been 26 years since the first optical detection and spectroscopy of single molecules in condensed matter. This area of science has expanded far beyond the early low temperature studies in crystals to include single molecules in cells, polymers, and in solution. The early steps relied upon high-resolution spectroscopy of inhomogeneously broadened optical absorption profiles of molecular impurities in solids at low temperatures. Spectral fine structure arising directly from the position-dependent 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, a variety of fascinating physical effects were observed for individual molecules, including imaging of the light from 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. In the room temperature regime, researchers showed that bursts of light from single molecules could be detected in solution, leading to imaging and microscopy by a variety of methods. Studies 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. All of these early steps provided important fundamentals underpinning the development of super-resolution microscopy based on single-molecule localization and active control of emitting concentration. Current thrust areas include extensions to three-dimensional imaging with high precision, orientational analysis of single molecules, and direct measurements of photodynamics and transport properties for single molecules trapped in solution by suppression of Brownian motion. Without question, a huge variety of studies of single molecules performed by many talented scientists all over the world have extended our knowledge of the nanoscale and many microscopic mechanisms previously hidden by ensemble averaging.

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  • Developments in experimental techniques such as ultrafast spectroscopy, single molecule spectroscopy, time-resolved microscopy and single particle imaging have enabled study of biological dynamics on increasingly small length and time scales, revealing processes necessary for living function that depend on a delicate interplay between quantum and classical physical effects.

    “Recently, developments in experimental techniques such as ultrafast spectroscopy [6], single molecule spectroscopy [7 -11], timeresolved microscopy [12 -14] and single particle imaging [15 -18] have enabled us to study biological dynamics on increasingly small length and time scales, revealing a variety of processes necessary for the function of the living system that depend on a delicate interpl”

    From The future of quantum biology (2018) · cites this paper as [7]

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Research works printed but not linked: 9

  1. [14]Zander C Enderlein J Keller RA Single-Molecule Detection in Solution: Methods and Applications Wiley-VCH Berlin 2002
  2. [28]Moerner WE Topics in Current Physics 44; Persistent Spectral Hole-Burning: Science and Applications Springer Berlin 1988
  3. [63]Elson EL Magde D Biopolymers 1974 13 1 27 4818131
  4. [65]Magde D Webb WW Elson EL Biopolymers 1978 17 361 367 4818131
  5. [68]Rigler R Widengren J 1990 Proceedings of Bioscience 3 180 183
  6. [83]Moerner WE Single Molecule Spectroscopy in Chemistry, Physics and Biology: Nobel Symposium 138 Proceedings Graslund A Rigler R Widengren J Springer-Verlag Berlin 2009 25 60
  7. [84]Rigler R Orrit M Basche T Single Molecule Spectroscopy, Nobel Conference Lectures Springer-Verlag Berlin 2001
  8. [85]Gräslund A Rigler R Widengren J Single Molecule Spectroscopy in Chemistry, Physics and Biology: Nobel Symposium 138 Proceedings Springer-Verlag Berlin 2009
  9. [202]Schlau-Cohen GS Wang Q Southall J Cogdell RJ Moerner WE Proc Natl Acad Sci U S A 2013 110 10899 10903 23776245 PMC3704035

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Authors
Moerner, W. E., Shechtman, Y., & Wang, Q.
Affiliations
Stanford University (US)
Corresponding author
Moerner, W. E.
Venue
Faraday Discussions
Published
2015
Volume
184
Pages
9-36
ISSN
  • 1359-6640 (ISSN-L)
  • 1364-5498
OpenAlex
W2119662414
Cited by
103
References
198
Citations by year
2026: 4 · 2025: 5 · 2024: 10 · 2023: 14 · 2022: 9 · 2021: 9 · 2020: 16 · 2019: 12 · 2018: 12 · 2017: 8 · 2016: 4
FWCI
0.80
Type
journal article
Language
en
Open access
Locations
  • Faraday Discussions (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of General Medical Sciences (R01GM085437, R01GM086196)
  • Basic Energy Sciences (DE-FG02-07ER15892)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
  • Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Spectroscopy and Quantum Chemical Studies
  • Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Photochemistry and Electron Transfer Studies
Keywords
single-molecule spectroscopy, single-molecule imaging, spectral diffusion, optical switching, single-molecule fluorescence microscopy, photoswitchable fluorescent proteins, super-resolution microscopy, single-molecule localization, molecular orientation, photodynamics, single-molecule transport
MeSH terms
Spectrometry, Fluorescence, Temperature, History, 20th Century, History, 21st Century

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