Single-Molecule Fluorescence Lifetime Imaging Using Wide-Field and Confocal-Laser Scanning Microscopy: A Comparative Analysis

  • Nazar Oleksiievets
  • , Christeena Mathew
  • , Jan Christoph Thiele
  • , Jose Ignacio Gallea
  • , Oleksii Nevskyi
  • , Ingo Gregor
  • , Andre Weber
  • , Roman Tsukanov
  • , Jorg Enderlein

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

A recent addition to the toolbox of super-resolution microscopy methods is fluorescence-lifetime single-molecule localization microscopy (FL-SMLM). The synergy of SMLM and fluorescence-lifetime imaging microscopy (FLIM) combines superior image resolution with lifetime information and can be realized using two complementary experimental approaches: confocal-laser scanning microscopy (CLSM) or wide-field microscopy. Here, we systematically and comprehensively compare these two novel FL-SMLM approaches in different spectral regions. For wide-field FL-SMLM, we use a commercial lifetime camera, and for CLSM-based FL-SMLM we employ a home-built system equipped with a rapid scan unit and a single-photon detector. We characterize the performances of the two systems in localizing single emitters in 3D by combining FL-SMLM with metal-induced energy transfer (MIET) for localization along the third dimension and in the lifetime-based multiplexed bioimaging using DNA-PAINT. Finally, we discuss advantages and disadvantages of wide-field and confocal FL-SMLM and provide practical advice on rational FL-SMLM experiment design.

Original languageEnglish
Pages (from-to)6454-6461
Number of pages8
JournalNano Letters
Volume22
Issue number15
DOIs
StatePublished - 10 Aug 2022
Externally publishedYes

Keywords

  • DNA-PAINT
  • fluorescence lifetime
  • fluorescence lifetime imaging microscopy
  • metal-induced energy transfer
  • single-molecule localization microscopy
  • super-resolution microscopy

ASJC Scopus subject areas

  • Bioengineering
  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics
  • Mechanical Engineering

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