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MICROSCOPE ON A CHIP: A new microscope fits onto a semiconductor chip smaller than a dime. Electrodes control the flow of fluid through a transparent channel (clear block). Light shines through the channel onto a series of holes in a metal layer that covers light-harvesting pixels in the chip. Objects in the fluid block the light from passing through the holes, which generates the image.
Courtesy of Changhuei Yang

Researchers hope that a new kind of small portable microscope may give health workers the ability to quickly and cheaply scan blood for tumor cells and life-threatening parasites.

What makes the microscope unique is the way it scans objects without lenses, and that it was inspired by a phenomenon that usually clouds vision instead of improving it.

A team from the California Institute of Technology (Caltech) has demonstrated that light-sensitive microchips like those found in digital cameras can produce high-resolution images of microscopic beads and worms about a millimeter long.

Writing in Proceedings of the National Academy of Sciences USA, they report that prototype lensless microscopes resolved details down to approximately 0.8 to 0.9 microns, or thousandths of a millimeter. (One millimeter equals 0.04 inch.) This is good enough to spot cancer cells, which measure 15 to 30 microns.

Here's how it works: Scientists shine light onto a liquid sample flowing through a narrow channel. Below the channel are a series of three-micron-wide apertures, or holes, punched through a layer of metal such as gold or aluminum. The light shines through the holes onto a semiconductor chip studded with a series of sensor pixels. Such chips cost about $10 a pop, says Caltech bioengineer and study leader Changhuei Yang.

Objects that float over the apertures block some of the incoming light received by the pixels, which reconstruct an image of the object based on the variations in light intensity across multiple apertures.

Yang says he was inspired by "floaters," the clumps of dead cells and other debris in the eye that are sometimes visible when staring at blue sky or other uniform sources of light. He says floaters are more common with age and in some eye conditions such as myopia.

Normally we see objects because the lens of the eye focuses an image onto the retina, often with help from corrective lenses. But floaters float right above the retina, where we can see them directly.

Conventional microscopes use lenses to magnify microscopic features for the eye to see, but lenses are hard to make small for use in portable handheld devices or for scanning lots of biological samples simultaneously, which would aid research.

With a chip-based microscope, "there's no lens to break," Yang says. "A clinician can stick this into his back pocket."

He says he sees the technology as the basis for rugged, iPod-size scanners capable of quickly diagnosing the presence of the blood parasites that cause malaria and sleeping sickness (human African trypanosomiasis), which are both endemic in sub-Saharan Africa.

Another possible application is scanning the blood of cancer patients for cancerous cells circulating in the body that may take root in other organs, a phenomenon known as metastasis that often signals a poor prognosis.

Right now, such cells can be collected on membranes, but transferring the cells to microscope slides is relatively complicated and expensive, says pathologist Richard Cote of the Keck School of Medicine of the University of Southern California, who was not part of the Caltech team but is working with Yang to develop a chip-based system to probe those samples directly.

Micron resolution is sufficient for basic tasks, he says, such as counting the number of potentially dangerous cancer cells. He says the lensless microscope "would be a way of actually disseminating the technology much more broadly."