"During the last twenty years, several different microscopes have been invented which can sharpen the eyes of biomedical scientists, showing more detail in an ever-tinier field of view. Our microscope, developed only recently in the UK, represents lateral thinking: we have broadened the field of view enormously, while keeping the acuity of a conventional microscope. This innovation allows a hundred-fold increase in the volume of the specimen from which sub-cellular detail can be obtained. Individual cells are seen in detail, but so also, for the first time, is their three-dimensional relationship to the whole organ or body.
The first confocal results of our optical 'mesoscope' were obtained in the last six months and announced in the 2012 Royal Society Leeuwenhoek Lecture and in a profile in the journal Science. There is now strong worldwide interest because the benefit is obvious in the images already published. There are many applications: here we will describe one of the most important as an example. One image (shown in the Case for Support) shows a median optical section of an entire mouse embryo five millimetres long. This is the first ever confocal image of such a large and thick specimen, with sub-cellular detail including individual Golgi bodies in the same image. The participants in this proposal include the two top UK labs in the field of mouse genetics, where researchers are eagerly seeking to use such images for phenotypic screening of human genes in mouse embryos, one of the most important and large-scale activities in modern biomedicine. We propose to also include in our project equally important but quite different areas of biomedical research where it is almost certain that the optical mesoscope will change the way that work is done.
This proposal to the MRC is to set up a centre, the Mesolab, and purchase two optical mesoscope systems at cost from the fledgling manufacturing company Mesolens Ltd (with which we have already worked successfully using our expertise in optical physics and software development to build the prototype confocal system). We are currently pursuing this work with modest but vital EPSRC Knowledge Transfer Agreement funding and support from the University of Strathclyde, as well as a single prototype Mesolens originally developed in the MRC Laboratory of Molecular Biology, Cambridge.
We will use the proposed MRC Mesolab facility to develop multi-photon scanning, high-resolution and fast camera imaging, and other imaging modes for the optical mesoscopes, with strong support in manpower, expertise and infrastructure from the University of Strathclyde and substantial input of material support and expertise and intensive design participation by the company, who will be our Project Partner. This development work will be completed within the first three years of the project, but even during this phase biomedical work will occur and there will be synergy between the collaborating biomedical users of the systems and the designers. This engagement (which the large microscope manufacturers have hitherto failed to achieve) will be a key feature of our project. In the second phase, the work will consist exclusively of optimisation of experimental procedures in each application to yield the greatest biomedical benefit.
We expect optical mesoscopy to be similar to the original development of the beam-scanning confocal microscope by the MRC, in providing a transforming technology for biomedical research. The creation of the Mesolab will allow scientists rapid access to this next generation microscopy method, which they are already seeking."