Say ‘microscope’ and most people think of the models they had in school. Those microscopes had lenses and used visible light (either natural light or a bulb of some kind). Generically they’re called optical microscopes. So what’s a microscope called if it doesn’t have any lenses? Try lens-free optical tomographic microscope. And this means what?
Biological samples, especially if they’re living, are difficult to put under a microscope. Microscopes based on visible light are relatively friendly to biological samples, but the wavelength of visible light is pretty big so that there are limits to the resolution of a typical optical microscope. Sure, new technologies such as the Atomic Force Microscope (AFM) or the Scanning Tunneling Microscope (STM) use electrons and other high-energy particles to work at very high resolution – atomic scale. They also ‘fry’ most biological samples. Living samples don’t stay that way for very long.
So scientists have worked for many decades to improve the optical microscope, and the lens-free optical tomographic microscope is one of the results.
The name’s a mouthful, so let’s spit it out one piece at a time: Lens-free means there are no glass lenses involved with enlarging the image. Optical indicates that the microscope uses visible light as the primary source of illumination. Tomographic is the really technical part. The microscope builds the image from ‘slices’ (sections) of the sample by illuminating from the sample from several different angles. In effect this is like a holograph, which is a three-dimensional recording of the light reflecting from an object.
In this case, researchers at the University of California Los Angeles (USA) and publishing in the journal Proceedings of the National Academy of Sciences, 19 April 2011, Paywall [Lens-free optical tomographic microscope with a large imaging volume on a chip] developed what they call an optical microscope on a chip. It works (simplified) like this: Start with a silicon chip about 15 cubic millimeters in volume on which is a super-sensitive digital sensor array (something like the CCD in a camera). The sample is spread about 4mm above this array in a very thin layer. Then the sample is illuminated by a rotating visible light source about 70 mm distant so that a multi-angle holographic representation can be captured in the sensor array. This produces the data, which when processed by specialized software, becomes the enlarged three-dimensional image.
The technical challenges in creating this new microscope technology were formidable, even though the component technologies such as tomography are relatively well known. While this prototype microscope still has a way to go before it becomes a production scientific instrument, it’s clear that it has many important advantages. It’s optical, which means that biological samples will remain intact while under observation. It’s relatively small, in fact, it can eventually become part of what scientists are calling a “lab on a chip” – the ability to analyze samples within the confines of a silicon chip similar to those now used in the computer industry. Despite its small size, this microscope actually has a very large sample volume, meaning it can analyze samples sized in millimeters at a time. This will lend itself to high capacity, high throughput analysis.
As is often the case, scientific instruments like this don’t get much attention. Then five, ten, fifteen years down the road and scientific breakthroughs start happening, because scientists can use a lens-free optical tomographic microscope to peer into the fundamentals of living biology.