Post date: May 22, 2012 11:35:7 AM
A new form of microscope which can produce results in seconds rather than hours - dramatically speeding up the process of drug development - is being developed by researchers at a Scottish university.
GLASGOW, SCOTLAND, UNITED KINGDOM (RECENT) (REUTERS) - Scottish-based scientists are creating a lens capable of showing three-dimensional images within cells and tissues at the same time as showing the whole organism, something which is currently impossible using a single imaging device.
The Mesolens, the only device of its kind in the world, will be able to capture detail in organisms which are too large to be examined satisfactorily by existing microscopes and offer a deeper insight into areas such as cancerous tissues and the cortex of the brain.
Dr Brad Amos, a Visiting Scientist at the Strathclyde Institute of Pharmacy and Biomedical Sciences, developed the lens with Strathclyde Chair of Biophotonics, Professor Gail McConnell.
The Mesolens employs confocal microscopy, an optical imaging technique used to increase optical discrimination of depth. In a confocal system, the light is focused to as small a spot as possible. A pinhole in front of the light detector allows the elimination of out-of-focus light. Both the pinhole and the light spot are scanned over the specimen to make an image. Nothing shows in this image if it lies outside the focal plane. The resulting image is free of blurring from structures above and below the plane of focus. From a series of such images (called 'optical sections'), the 3D structure of the specimen can be reconstructed in a computer For this method to work, the lens has to have a shallow depth of field to blur out the layers that aren't needed. This approach was pioneered in the mid-1980s and is now widely used across the world, allowing 3D models of organisms to be built, creating pictures that can be zoomed in towards in incredibly fine detail.
The problem with existing technology is that achieving the shallow depth of field required to blur out the other layers of a subject means limiting the size of the image itself. The existing confocal microscope produces images that are typically only one fifth of a millimetre across.
Amos and his team set about building a microscope that was able to visualise high levels of detail on a larger scale. Unfortunately, the new lens has to be very large, and proportionally large mirrors must be used to scan the beam of light. But luckily such mirrors do exist: they are made for large-scale laser scanning for military and industrial purposes, but have never been applied previously to medicine.
"They're very lightweight mirrors, they're manufactured using beryllium and then they're back-thinned with this very elegant kind of birdswing structure to try and reduce overall mass where it's not actually required but with very good optical surfaces to reflect that very large laser beam, to scan within the specimen, and so for us having low jitter on those mirrors, in other words good reproducablility on each subsequent scan was absolutely essential," said McConnell.
The microscope makes it possible to focus on different depths of a specimen in unprecedented resolution in large images, allowing the observer to zoom within the captured image to observe subcellular detail.
"What we have here is a combination of the confocal principle, which is now very well established and widely used, with a lens design that is totally novel and which is really bridging a gap between microscopy and macrophotography," explained Amos.
He added: "It can image detail at the level of half a micron - that is one two-thousandth of a millimetre. That means that when we combine that with this large field of view, the large coverage of the lens, we can capture both cellular detail in an organism and the anatomy."
Where existing microscopes have lenses up to three centimetres long, the Mesolens is a massive half a metre, which means it can capture a specimen as large as a mouse embryo in a single shot. And whereas a confocal microscope can view up to 0.22 millimetres below the surface of a specimen, provided it is translucent enough, the Mesolens plumbs depths of up to 3 millimetres. The final effect is a 3D picture that allows one to zoom in to see individual cells and even the detail within them. The microscope could save biologists the effort of patching together hundreds of small high-resolution images if they want a larger one, and can also reach deeper than normal.
The global health challenges of the 21st century demand new and powerful treatments but the process of drug discovery and delivery is often time-consuming and costly. The confocal Mesolens can be trained simultaneously on or inside an individual cell and the full organism.
McConnell said it offers great diagnostic possibilities for doctors.
"Rather than being able to see a very small volume within a large object, it's being able to see that small volume in very fine detail but also then look at the whole organism with the same fine detail. So you've got the fine detail across the whole organism, not just within a very small volume. Now that starts to inform about diseases and understanding how diseases progress," said McConnell.
The microscope will be able to produce results in seconds rather than hours, dramatically speeding up the process of drug development.
Researchers world-wide are now enquiring about the Mesolens and the Strathclyde team plan to bring it into production as a research tool soon. Pathologists in Glasgow are also considering fast-tracking the instrument into cancer research.