Pushing Microscopy Beyond Standard Limits

Using Caltech's system, an ordinary microscope can capture 100 times more information per image 

Thanks to research being conducted at the California Institute of Technology, regular microscopes could soon be capable of much higher-resolution imaging. Instead of making changes to the microscopes’ optics, the Caltech researchers are instead focusing on using a computer program to process and combine images from the devices.

Such a system could greatly improve the efficiency of digital pathology, in which specialists need to review large numbers of tissue samples. By making it possible to produce robust microscopes at low cost, the approach also has the potential to bring high-performance microscopy capabilities to medical clinics in developing countries.

"In my view, what we've come up with is very exciting because it changes the way we tackle high-performance microscopy," says Changhuei Yang, professor of electrical engineering, bioengineering and medical engineering at Caltech.


The main hardware change to an existing microscope involves installing an array of about 150 LEDs beneath the stage, in place of the regular light. Using each bulb in that array one at a time, 150 images are then acquired of the sample that’s being viewed. In each image, the light is originating from a slightly different (and known) direction. The computer program then stitches all of those images together into one cohesive image of the sample.

A rendering of the Caltech system

That composite image represents not only the light’s intensity, but also the light phase information (related to the angle at which the light travels) for each of the sub-images. Using that light field data, the program allows users to zoom in on any part of the overall image, while still being able to make out details. It’s also able to digitally correct for flaws, such as areas which are initially out of focus.

Ultimately, images produced by the system contain 100 times more information than those produced by an unaided microscope. Additionally, it creates images with both the wide field of view of a lower-powered lens, and the resolution of a stronger one. Ordinarily, microscope users have to choose between getting wide shots of samples in which details can’t be made out, or detailed shots of just a small part of the sample – sort of like using either a wide-angle or close-up lens on a camera.

The microscope setup, along with an image taken with a traditional 2X lens (top right) and a composite image of the same sample taken using the new system

It should cost approximately US$200 to add the technology to one existing microscope. The scientists hope that it could be used in applications such as digital pathology, wafer inspection and forensic photography, or by medical clinics in developing nations.
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Write by: RC - Thursday, August 1, 2013

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