At FLIM impact (Episode I)

What has been the impact of fluorescence lifetime imaging microscopy to science and to the biomedical community in particular? Is FLIM a niche technique, one of those techniques that always promise but never deliver?

The top 10 most cited papers

Excluding reviews, the list of the top 10 most cited papers, albeit representing a very narrow window on the impact that FLIM had on the broader community, is rather instructive. Do consider, we are missing all those papers where FLIM was used but not cited in title or abstract. Most of the top 10 is made of applications to cell biochemistry, demonstrating the potential and the impact that fluorescence lifetime has. FLIM helped to understand how signalling work in living cells and animals, helped to identify drugs and to study disease. Some of the top cited papers are more technical, such as Digman’s paper on the phasor-transform or Becker’s paper on TCSPC widely cited because of their influence on contemporary FLIM techniques from a perspective of data analysis and technology. Other papers date back to the initial years of FLIM with applications to biochemistry. Overall, from this list, we understand (if more evidence was needed) that FLIM had a deep impact on the understanding of cell biochemistry albeit, historically, FLIM has been limited to the specialist laboratory.

I would like to highlight also another small observation, perhaps just interesting for the specialists, and not visible from other bibliometric analyses. Tom Jovin and a group of scientists trained by him (e.g., Dorus Gadella and Philippe Bastiaens) left a significant footprint in the field, directly driving biomedical relevant applications while pushing, at the same time, technological or methodological developments. Many others are linked to this ‘school’ directly or indirectly, scientists that use/develop a microscope to do biochemistry.

  1. Mapping temperature within cells using fluorescent polymers by Okabe and colleagues (2012) from Uchiyama’s laboratory and published in Nature Communications, where FLIM was used to map temperature within cells using fluorescent polymers as temperature sensors. (442)
  2. Phasor analysis by Michelle Digman and colleagues, from the laboratory of Enrico Gratton (2008) published by Biophysical Journal. The phasor-based analysis, in different flavours, has become quite popular nowadays. (406)
  3. An in vivo FLIM-based analysis of calcium dynamics in astrocytes by Kuchibhotla and colleagues from Bacskai’s laboratory (2009) published in Science. (353)
  4. The study of Calmodulin-dependent kinase II activity in dendritic spines by Lee and colleagues from Yasuda’s laboratory (2009) published in Nature. (351)
  5. One of the first FLIM papers by Lackowicz, published in 1992 in PNAS, where they applied the methodology, yet to be fully established, to the study of free and bound NADH. (339)
  6. One of the first biochemical applications of FLIM, where Gadella and Jovin applied the new tools to the study of EGFR oligomerization (1995), published in the Journal of Cell Biology. (323)
  7.  A 2004 paper, where Becker and colleagues present the TCPSC instrumentation that would become a commercial success, published in Microscopy Research and Technique. (321)
  8. The application of FLIM and molecular motors to study viscosity of the cellular environment by Marina Kuimova and colleagues, from the laboratory of Klaus Suhling published on JACS in 2008. (319)
  9. The development of a drug interfering with the interaction between KRAS and PDEdelta published Zimmermann and colleagues with the laboratory of Philippe Bastiaens and published by Nature in 2013. (291)
  10. The interaction between PKC and integrin shown by Ng an colleagues from Parker’s laboratory in 1999 by the EMBO Journal. (277)


Tool: Web of Science

Search term: “FLIM” and “fluorescence lifetime imaging microscopy”

Filter: Article

Note: FLiM is a component of the flagella motor and it shows up in the searches. I could not eliminate this ‘false positive’ but it is my assumption that it is not changing  the following discussion.

Citations (in parenthesis) as in April 2019.

Any bibliometric analysis is very limited in scope, certainly this very narrow search. This is just a blog post, one observation done just to trigger a discussion for those curious people about the topic.


Author: Alessandro

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