New Molecular Solutions in Research and Development for Innovative Drugs

Optical mesoscopy with a new giant lens

Gail McConnel, Centre for Biophotonics, SIPBS, University of Strathclyde, Glasgow, UK.

Optical lenses reached the limit of resolution set by the wavelength of light more than a century ago. However, no attempt was made to achieve the maximum resolution in the case of low-magnification lenses, probably because the visual image would then have contained detail too fine to be perceived by the human eye (which cannot separate lines of less than 1 minute of arc apart).

Currently available lenses of less than 10x magnification are of simple construction and their numerical apertures (which determine their resolving power) are 0.2 or less, as compared with 1.3 or more in high-power lenses. They are perfectly adequate for the eye or a standard camera, but in the 1980s, confocal microscopy and improvements in camera resolution revealed a need for better low-power lenses: many researchers found that thin confocal optical sections could not be obtained at 4x.

Researchers at Strathclyde have collaborated with Dr Brad Amos (MRC Laboratory of Molecular Biology) to develop a novel lens system called the Mesolens, which achieves an N.A. of nearly 0.5 at a magnification of only 4x. When compared with a standard 4x objective, its lateral resolution is 2.5 to 5 times better and its depth resolution (which is vital for confocal or multi-photon microscopy) is 10x better.

This lens provides, for the first time, good optical sectioning of specimens as large as entire 10 day mouse embryos (5mm long) with subcellular detail in every developing organ. The lens is difficult to make because of the need for a higher degree of aberration control than in any standard camera lens and it is too large (optical train 50cm x 7 cm) to fit on any standard microscope as well as having too great an aperture size for standard confocal apparatus.

A confocal imaging system based on the Mesolens has been developed in the University of Strathclyde, Glasgow, UK. Through the Next Generation Optical Microscopy Initiative, the UK government has made funds available for a facility in Strathclyde for the development and application of Mesolenses in biomedical science, including super-widefield, confocal, multi-photon and light-sheet imaging modes.  Progress in the creation of the facility, recent data and some future work will be presented.