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Engineers at the California Institute of Technology have designed a dime-sized lensless microscope able to capture high-resolution images of cells and pathogens. The low-cost, portable technology could be an ideal tool for use in developing countries, according to the paper, published online today (July 28) in the Proceedings of the National Academy of Sciences.



Despite the trend towards miniaturization evident in the popularity of lab-on-a-chip systems, attempts to make a miniature microscope have been stymied because of the expense of creating small, precise lenses and the space required for light to reshape between lenses.

"You don't really need all those fancy lenses to do microscopy," said Changhuei Yang, assistant professor of bioengineering at CalTech and senior author on the paper. Yang and his colleagues did away with lenses altogether and created an "optofluidic microscope," a tiny instrument that combines the technology of digital cameras with small-scale fluid flow, microfluidics, to capture images of cells and small organisms.

The microscope's simple design took four years to develop. A charge-coupled device (CCD) sensor, used in most digital cameras, forms its base. The sensor is coated with a layer of metal that is then punched through with tiny holes, each about 1?m wide. Punching the holes "took the longest time," said Yang. "We kept damaging the sensor chip underneath." But the holes were vital: Each acts as an artificial pixel, so the resolution of the image depends on the size of the holes.

The engineers then had to perfect a microfluidics channel for atop the holes. It was not easy to make liquid samples flow smoothly through the channel instead of clotting, said Yang. In the end, the team designed two versions of the microscope: one using a gravity-driven flow that works best for elongated specimens, like C. elegans, and another that employs an electric charge to create a uniform flow, which prevents samples like cells or spherical microbes from rotating while moving through the channel.

With either version, the sample is lit from above -- even sunlight is a sufficient light source. As the sample travels across the channel, the CCD sensor records either light or shadow passing through each hole. Because the holes are punched at a diagonal instead of a straight line, the images overlap slightly, and are pieced together on a display panel. "The computation involved is very trivial," said Yang.



Yang believes the micro-microscope will be particularly useful for scientists in developing countries. "The complete system would be the size of an iPod," said Yang. Researchers would be able to carry it in their shirt pocket and pull it out to detect malaria in a blood sample or giardia in a water supply. Additionally, because of its inexpensive parts, Yang expects the microscope to be mass-produced for around $10 apiece. He is currently in negotiations with several companies interested in making the chip.

But the technology has limitations. Samples must be fluid, and the microscope does not magnify an image. "This method is highly specialized and, as an example, cannot image objects that are tumbling or rotating," wrote Juergen Kreuzer, a professor of physics as Dalhousie University, in an Email. He also emphasized that the sample must be thin enough to transmit light. Kreuzer, who holds patents on Digital In-line Holographic Microscopy, another alternative to traditional microscopy, was not involved in the study.

Currently Yang and his team are working on two additions to the technology -- using the microscope for immunofluorescence and for phase contrast imaging. "You can actually build five of these microscopes in one microfluidic channel," said Yang, "and have a multi-fluorescent image of the object without having to change a carousel." Labs could someday own "tens or thousands" microscopes instead of just a few, he noted, and process large numbers of samples all at the same time.



First image- The optofluidics microscope on a chip

Second image- Image of C. elegans captured by the microscope

Third image- A rendering of the microscope design