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Tweaks turn microscope into billion-pixel imager

BioPhotonics
Oct 2013
PASADENA, Calif. – Converting a relatively inexpensive conventional microscope into a billion-pixel imaging system could improve the efficiency of digital pathology and provide robust microscopes to medical clinics in developing countries.

The physical limitations of microscope objectives have hindered improvements to conventional microscopes for several years. Microscope makers have tackled these limitations by using ever-more-complicated stacks of lens elements in microscope objectives to mitigate aberrations. Even so, the physical limitations have forced a trade-off between high resolution with a small field of view, or low resolution with a large one.

Now, engineers at the California Institute of Technology (Caltech) have devised a system that combines the field-of-view advantage of a 2× lens with the resolution advantage of a 20× lens. The new system – which costs only about $200 to implement – produces images with 100 times more information than those from conventional microscope platforms.


This artist’s rendering of Caltech’s new microscopy setup shows one element of an LED array illuminating a sample. Courtesy of Yan Liang and Guoan Zheng.


“We found a way to actually have the best of both worlds,” said Guoan Zheng, lead author and initiator of the approach, developed in professor Changhuei Yang’s lab. “We used a computational approach to bypass the limitations of the optics. The optical performance of the objective lens is rendered almost irrelevant, as we can improve the resolution and correct for aberrations computationally.”

An advantage of the approach is its hardware compatibility, Zheng said. “You only need to add an LED array to an existing microscope. No other hardware modification is needed. The rest of the job is done by the computer.”

The system acquires about 150 low-resolution images of a sample, each corresponding to one LED element in an array; light coming from known different directions illuminates the sample. A novel computational approach, Fourier ptychographic microscopy (FPM), then stitches the low-res images together to form a high-resolution and more complete picture of the sample’s entire light field.

“What this project has developed is a means of taking low-resolution images and managing to tease out both the intensity and the phase of the light field of the target sample,” said Yang, a professor of electrical, bioengineering and medical engineering at Caltech. “Using that information, you can actually correct for optical aberration issues that otherwise confound your ability to resolve objects well.”

The large field of view could be particularly useful for digital pathology, where the typical process of using a microscope to scan the entirety of a sample can take tens of minutes. Using FPM, the whole thing can be imaged all at once instead of in parts. And, because it acquires a complete set of data about the light field, it can computationally correct errors – such as out-of-focus images – so samples do not need to be rescanned.

“It will take the same data and allow you to perform refocusing computationally,” Yang said.

The method could be used in everything from hematology to wafer inspection to forensic photography, they say.

The work appeared online in Nature Photonics (doi: 10.1038/nphoton.2013.187).


GLOSSARY
forensic photography
The application of ultraviolet, x-ray, infrared and conventional photography to law enforcement.
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