Time-resolved Microscopy and Correlation Spectroscopy

This is a guest post from Jennifer Francis, PhD Student in the group. When group members go to conferences or courses, they have to write a travel blog post.

I recently attended the 8th European Short Course on “Time-resolved Microscopy and Correlation Spectroscopy” at PicoQuant headquarters in Aldershof-Berlin; specifically to learn about the principles and application of FRET, FLIM, and FCS to the Life Sciences. A day prior to this microscopy course, I also attended the 14th SymPhoTime Training Day. As well as discussing problems and applications of the SymPhoTime64 software with other users, I also had the opportunity to speak with a programmer of the software, who demonstrated many new features and assisted with analysis of my own FCS measurements at a computer station. My mornings generally started with passing an incredible sculpture of two heads, before arriving at the Max Born Institute for lectures delivered by scientists in the field of time-resolved microscopy, including Professor Jörg Enderlein.

two heads

Landmark of Berlin-Aldershof: Kopfbewegung – heads, shifting.


After a Flammkuchen, I participated in afternoon practical microscopy sessions, where I got the chance to experience the commercially available super-resolution microscope: MicroTime 200 STED, which was awesome. Not only did we see this cutting-edge instrument in action, resolving structures below the diffraction limit, but we also had a peek inside the operating laser boxes! Whilst at the STED station, members of GATTAquant informed us about nanorulers, which are new standards for super-resolution microscopy. Another highlight of this workshop was the demonstration of the Zeiss LSM 880 with Airyscan, which boasts 32 detectors. There were a total of 42 participants on this course, both from academia and industry, including microscope representatives from Olympus, Zeiss, Leica, and Nikon. The consensus take home tip from all participating microscope companies was to always match the refractive index of the objective with that of the sample and to adjust the correction collar to take into account coverslip thickness.


A postcard from Israel

Originally published on the University of Liverpool news website.

“I sat next to the taxi driver. We started talking. The ride from my hotel on Ben Yehuda Street in down town Tel Aviv to the Bar Ilan campus takes about 45 minutes. ‘Liverpool’, the taxi driver said, ‘I was there several times in the 1950s; I was a sailor.’

I was sufficiently intrigued to ask him his age. ’80 in six months,’ was his reply. He, who was older than his country, had no shortage of stories and the 45 minutes went quickly. When the Suez crisis broke in 1956, he was in Odessa, Soviet Union, on a tanker ship supposed to bring coal to Israel. I also learnt that Russia is 800 times larger than Israel.

I had spent the previous three days at Tel Aviv University, closer to the city centre, starting the week (on Sunday, of course) by giving a seminar in the Centre for Nanoscience and Nanotechnology. In Bar Ilan, I visited and gave a seminar at BINA, the Institute for Nanotechnology and Advanced Materials. The aim of my 10 days visit, funded by the British Council, is to develop scientific collaborations with Israeli colleagues and so, beyond taxi drivers, I met biologists, physicists and chemists working on areas more or less related to my own research interests, i.e. the preparation of nanoparticles and their applications in biology, especially for imaging of biomolecules and tracking of cells.

The discussions, prompted by my somewhat provocative, or ‘iconoclastic’ as one distinguished Israeli colleague put it, seminar were not limited to nanoscience but extended to the reproducibility crisis, changes in the scientific publishing landscape, and the opportunities that the internet offers to improve the way we do science by increasing the sharing of ideas (including critiques) and the sharing of data.

The tree of knowledge and electronics, and, Ouri’s corner by Asaf Lifshitz.

The tree of knowledge and electronics, and, Ouri’s corner (detail), by Asaf Lifshitz. Picture by Raphaël Lévy.

This week, I complete my journey by visiting a third major Israeli institution, and giving two more seminars, at the Technion, situated in Haifa, also on the coast, an hour by train North of Tel Aviv. The stunning campus is decorated by a number of sculptures. The first seminar takes place in the Institute of Biomedical Engineering and the second in Chemical Engineering.

During these ten days I will have met over 50 scientists at different stages of their careers and I hope that there will be some lasting links; maybe one of the younger ones will join my lab in Liverpool, or, an international collaborative project will take shape with more established colleagues? Whatever happens, if I go again, I’ll send you another postcard from Israel.”

How do I know if an article is good? an #ACSBoston tale

This week I attended the fall meeting of the American Chemical Society in Boston. A little meeting of about 14,000 attendees. I was speaking in a symposium with an impossibly long title but which turned out to be good fun and interesting; big thanks to the organisers: Kimberly Hamad-Schifferli, Clemens Burda and Wolfgang Parak.

IMG_0117I spent most of my time in that symposium but also went to a few other sessions which tackled questions surrounding the ways we do and communicate science. I learnt a bit more about the activities of the Center for Open Science and the platform they offer to researchers to organise, plan, record and share their work (and I was even offered a T-shirt). Probably the best lecture I heard – and certainly the most entertaining – was in a science communication session “The poisoner’s guide to communicating chemistry” by Deborah Blum (now I really need to read her book).

I joined a session with the promising title of “Scientific Integrity: Can We Rely on the Published Scientific Literature?“. Judith Currano (Head of the Chemistry Library, University of Pennsylvania) discussed how to help students evaluate the quality of scientific articles; I reproduce the abstract below (italics and bold mine):

This paper, by a chemistry librarian and a professor who edits an online journal, frames the challenges facing scientists at all levels as a result of the highly variable quality of the scientific literature resulting from the introduction of a deluge of new open-access online journals, many from previously unknown publishers with highly variable standards of peer review. The problems are so pervasive that even papers submitted to well-established, legitimate journals may include citations to questionable or even frankly plagiarized sources. The authors will suggest ways in which science librarians can work with students and researchers to increase their awareness of these new threats to the integrity of the scientific literature and to increase their ability to evaluate the reliability of journals and individual articles. Traditional rules of thumb for assessing the reliability of scientific publications (peer review, publication in a journal with an established Thomson-Reuters Impact Factor, credible publisher) are more challenging to apply given the highly variable quality of many of the new open access journals, the appearance of new publishers, and the introduction of new impact metrics, some of which are interesting and useful, but others of which are based on citation patterns found in poorly described data sets or nonselective databases of articles. The authors suggest that instruction of research students in Responsible Conduct of Research be extended to include ways to evaluate the reliability of scientific information.

Now the problem of (rapidly) evaluating the reliability of an article, especially for new researchers in a particular field is a serious and acute one, so I fully approve the author’s suggestions.

However the entire paper is based largely on a false premise: the idea that it is the “introduction of a deluge of new open-access online journals” which creates this reliability problem. This is hardly the case. The difficulty in identifying poor articles is not the deluge of open access journals nor is it predatory publishing. The growth in the volume of publications is not particularly related to open access and predatory publishing can be easily identified (with a little bit of common sense and a few pointers). The abstract (and to a lesser extent the talk) also conflates the evaluation of the reliability of a journal (an impossible task if you ask me) and the reliability of an article (an extremely onerous task if you ask me, but more on this later). Do I need to comment on the “rule of thumbs“?

I do teach third year undergraduate students on a similar topic. I ask them this same question: “how can you evaluate the validity of a scientific article?”. I write their answers on the white board; in whatever order, I get: the prestige of the University/Authors/Journal, the impact factor, the quality (?) of the references… I then cross it all. I show the Arsenate DNA paper published in Science, the STAP papers published in Nature. I try to convince them that no measure of prestige can help them evaluate the quality and reliability of a paper, that the only solution they have is to read the paper carefully and critically analyse the data. If necessary, discuss it with others. If necessary ask questions to the authors.

Of course, reading carefully takes time, but there is (currently) no alternative. There is absolutely no reason to think that a paper is reliable because it is in an high impact factor journal. The Scottish philosopher David Hume (1771-1776) wrote that “A wise man proportions his belief to the evidence”…and should “always reject the greater miracle.” Many articles in high impact journals resemble such miracles and eventually turn out to be irreproducible.

The second part of my own scientific presentation focused on our ongoing SmartFlare project. On the last slide, it featured the David Hume quote as well as an updated 21st version (see below).


With the PubPeer browser extension, you can immediately see, on the journal page (or anywhere else the article is cited) if there is an existing discussion at PubPeer

There is however something simple that we can do immediately to make it easier for every body to evaluate the reliability of individual articles: sharing our critiques (positive or negative) of articles we read. If we all commit to use PubPeer and start sharing at least one review per month, this will go a very long way towards generating open discussions around articles. It will obviously not alleviate the need to read the articles and the reviews critically, but it will crowd source the evaluation and this can be very powerful (it is the model of SJS, ScienceOpen, F1000).


Are StickyFlares smarter than SmartFlares?

Update (19/08/2015): Dave Mason has posted a detailed critique of this paper at PubPeer

Update (19/10/2015): We have submitted a response to this paper as a Letter to the Editor of PNAS. It is currently available as a preprint.

Update (16/11/2015): Inder Verma, Editor of PNAS, has decided that our letter “does not contribute significantly to the discussion of the StickyFlare paper.”

A quick post before I take off to Boston tomorrow for the American Chemical Society national meeting. I informed Chad Mirkin of my Monday talk where I will discuss the SmartFlares (talk on Monday, abstract). In his reply, he pointed me to a contributed PNAS paper they published in July on StickyFlares (Links: article, Northwestern press release). The questions that this technology raises are the same as the ones raised by the SmartFlares, as discussed in a previous post. Eight years after the initial NanoFlare paper, they are still not answered in this new article.

Check the latest results of our SmartFlare studies on the open notebook and data repository.

Elena at the MRS

I am catching up after an holiday break. I have not spoken yet with Elena who was at the MRS spring conference in San Francisco, but, thanks to blogging, I can tell she seemed to have had a good experience.

Fellow blogger Mary Nora Dickson enjoyed Elena’s first oral presentation at an international conference:

peptide SAMs on gold NPs

Elena Colangelo spoke today in GG about her work on whether the curvature of gold NPs will affect the conformation of adsorbed proteins. This is an important topic, with wide ranging applications from drug delivery to energy. She found that more highly curved NPs inhibit hydrogen bonding, decreasing the amount of beta sheet secondary structures. This work will help to inform future investigations seeking to modify nanoparticles with functional ligands. Thanks!

Thank you Mary for the report and congratulations to Elena 😉

Elena attended some great talks:

Carlo Montemagno’s talk

What an inspiring talk!

On the last slide of his talk, Michelangelo’s quote: The greatest danger for most of us is not that our aim is too high and we miss it, but that it is too low and we reach it

He gave an overview of the cutting-edge projects (in the general areas of environment, health and energy) going on in his lab, IngenuityLab.

The project that fascinated me the most is the 4D Printer, where the fourth dimension is intended to be the functionality of the complex system built up by single molecules. The general concept is the precise assemble of the functional building blocks found in nature to give new functionalities to the system, where these functionalities are meant to address issues regarding energy, environment and human health.

It may sound too futuristic, but would you ever have imagined having your smartphone, as it looks like today, 10 years ago?

Neelkanth Bardhan’s talk

I had the pleasure to listen to Neelkanth Bardhan’s talk, Gold MRS graduate student awardee, at Symposium GG.

First, I want to say that I found his presentation very clear and easy to follow, nice layout of the slides.

He first went through the motivation of his work: there is the clinical need of safer (compared to X-rays) and less expensive (compared to MRI) detection technologies. He then presented his work aiming to answer this need: developing a biologically-templated nanomolecular probe for high-resolution in vivo sensing and detection. His modular probe is constituted of M13 virus coating single-walled carbon nanotubes (SWNTs). To this construct desired fluorescent dyes and specific targeting ligands can be attached. His results in vivo have shown how this probe is able to target tumours and can be used during real-time surgical intervention.

More details on his work and successful applications of this probe can be found here.

Elena to present at the MRS spring meeting in San Francisco

Just in case the last post made you think it is only the boss who travels… Elena Colangelo, who is spending two years of her PhD project in Singapore, will be giving a selected talk at the MRS Spring meeting in San Francisco, symposium GG: Foundations of Bio/Nano Interfaces─Synthesis, Modeling, Design Principles and Applications.

She will be speaking on Friday 10th of April. The title of her talk is: Characterizing the Organization and Investigating the Conformation of Peptide Self-Assembled Monolayers on Gold Nanoparticles: An Experimental and Computational Approach. The abstract can be found on the program page.

Not only, as the Rapha-z-lab rule demands will she write here about her meeting experience (she has done this beautifully before), the talks will apparently be recorded so you will be able to watch it through MRS OnDemand shortly after the conference!