Since 2010, Dr Brad Amos, Mr Es Reid, Dr John Dempster and Professor Gail McConnell have collaborated on an optical mesoscopy project that uses a new giant lens – the Mesolens – to create three-dimensional images of large volume specimens with sub-cellular detail. This page details the pre-history to the creation of the Mesolab.
In May 2011, the Mesolens made the long journey from Cambridge to Strathclyde on a very stormy day. With genuine fear on my part that I would drop the only Mesolens in existence, we began setting up the Mesolens in its new home in the Centre for Biophotonics. Thankfully it had not suffered from the trip, and when we set it up as a camera lens it remained fully functioning. That meant it was now time to get to work.
Together with Dr John Dempster, who wrote the ‘Mesoscan’ software to control both the large scanning galvos and Mr Ged Drinkwater, who built the controlling electronics for the galvos, Brad, Mr Rumelo Amor and I obtained the very first scanning confocal images using the Mesolens in January 2012. This timing was not by chance: in February 2012 Brad was awarded the Leeuwenhoek Medal by the Royal Society and gave a prize lecture, the crescendo of which was the first public presentation of the confocal Mesolens images. With the prototype system now in full swing, we began to develop complementary mesoscopy tools and techniques, and to improve the stability of the system. New applications began to emerge, and in March 2012 ‘Science’ published an article on Brad and the Strathclyde confocal mesoscopy work. Things were going well, but we couldn’t have predicted what happened next.
In May 2012, RCUK launched a call for funding through a new joint Next Generation Optical Microscopy Initiative, led by the Medical Research Council (MRC), and with co-funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). The aim of this call was to support 10 or more strategic and innovative partnerships for up to five years during a period of rapid expansion, improvement and establishment of new microscopy technologies. Funding was available for:
– Next generation microscopes, especially super-resolution platforms Facility support – including capacity building support for enabling roles such as technical innovators and support staff.
– Partnership development funding to bring together inter-disciplinary research excellence to foster collaborations to develop technological innovation. Applicants can request small innovation seed-funding (£50-100k per activity) to support early partnership activities e.g. developing new probes and approaches for sample preparation, optics, sensors or software for image-capture.
The words “especially super-resolution” permeated my mind, because what we wanted to do was the very opposite. To quote from our submitted application:
We propose to create a facility unique in the world that will give the biomedical research community access to optical mesoscopy, a new and highly sought-after technology that is poised to revolutionise imaging.
We have, in collaboration with Dr Brad Amos FRS (MRC & Mesolens Ltd), developed a new imaging method which we have named ‘optical mesoscopy’ to convey its simultaneous function as both a microscope and a macroscopic imaging system. Giving sub-micron resolution across a 6 mm field of view, the optical mesoscope provides a hundred-fold increase in the volume from which high-definition information can be collected, allowing biomedical scientists to study thousands of cells in an intact organ or tissue milieu instead of a few cells in isolation in vitro. The new microscope will abolish time-consuming and laborious stitching of hundreds of images and, because of its high optical throughput, will reduce radiation dosage in fluorescence work and permit single-cell bioluminescence imaging. Preliminary published results are extraordinary, and indicate that this will have major impact throughout biomedical research.
1. To establish a facility to evaluate a new form of optical microscopy. The proposed ‘Mesolab’ will comprise of two optical mesoscopes that will be built and made available with priority to the project participants but also to the wider scientific and medical communities. The University of Strathclyde will house the facility in the new £36M Hamnett Wing of the Arbuthnott Building and will allow use of its high- volume data channel. In addition, the University will provide matched-funding to support a technical assistant to run the Mesolab facility full-time. There will be a steering committee consisting of the project applicants, Project Partner, all work- package participants and other non-user appointees, who will assess and prioritise their own use of the Mesolab facility and that of external researchers.
2. To develop the optical mesoscopy approach (which has this year been extended to include confocal scanning) further into varied forms, each optimised to answer key questions in biomedical research. We have brought together in this application leading researchers who will further develop optical mesoscopy to include fast wide-field fluorescence recording, confocal and multi-photon laser scanning, digital scanning lightsheet and fluorescence lifetime imaging methods. 3. To organise staff and equip the Mesolab facility in such a way that it may continue to be a world centre for optical mesoscopy after the requested MRC support ends. There will be long-term demand for this facility from users in diverse fields stimulated by the work that will be done in the present proposal.
I called the MRC and discussed our ideas with them. To our delight, they suggested that we could fit within the call and so we began work on the proposal. With a deadline of six weeks (one of which I spent in Kranjska Gora for some ill-timed alpine climbing) the pressure was on to get something sensible together. Thankfully we weren’t short of people keen to get involved and support the project (more details on that later). The proposal was submitted on 2nd July and then we waited. And waited. The “good news” from the MRC sent in November wasn’t that we received funding but that their initial budget of £18M was increased. Good, but not the great news we were hoping for. We continued to wait, tempers became frayed (well, mainly my temper). In early December, word started spreading about who wasn’t funded, but no information was forthcoming from the MRC about our proposal. After much toiling and moiling I called the Programme Manager, who said that we should hear something very soon. She was right: within a few days we learned that our project was indeed funded. Needless to say we were all delighted and excited about the project.
The project started ‘formally’ on 13th February 2013, and work is already underway in both appointing new staff and creating the Mesolab facility in SIPBS. This blog is intended to keep (relatively) up to date on developments at Strathclyde relating to the Mesolab and the outputs.
Press release from the MRC: http://www.mrc.ac.uk/Newspublications/News/MRC008999
Selection of images of projects funded by the call: http://www.flickr.com/photos/next-gen-microscopy/
University of Strathclyde press release: http://www.strath.ac.uk/press/newsreleases/headline_694434_en.html
Dr Brad Amos FRS: http://www2.mrc-lmb.cam.ac.uk/group-leaders/emeritus/brad-amos/
Brad’s Leeuwenhoek Medal lecture online (Royal Society). Lasts approximately one hour: wine and popcorn recommended by Brad himself: http://royalsociety.org/events/2012/optical-microscope/
Professor Allister Ferguson: http://phys.strath.ac.uk/information/acadstaff/allister.ferguson.php